[go: up one dir, main page]

WO1998056354A2 - Preparations retard a unites multiples et procedes permettant de les preparer - Google Patents

Preparations retard a unites multiples et procedes permettant de les preparer Download PDF

Info

Publication number
WO1998056354A2
WO1998056354A2 PCT/EP1998/003103 EP9803103W WO9856354A2 WO 1998056354 A2 WO1998056354 A2 WO 1998056354A2 EP 9803103 W EP9803103 W EP 9803103W WO 9856354 A2 WO9856354 A2 WO 9856354A2
Authority
WO
WIPO (PCT)
Prior art keywords
polymer
water
release
extrudates
dosage forms
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.)
Ceased
Application number
PCT/EP1998/003103
Other languages
German (de)
English (en)
Inventor
V.-Ranga Rao Kanikanti
Roland Rupp
Erich Brendel
Claus Weisemann
Ernst Chantraine
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.)
Bayer AG
Original Assignee
Bayer AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer AG filed Critical Bayer AG
Priority to AU84349/98A priority Critical patent/AU8434998A/en
Publication of WO1998056354A2 publication Critical patent/WO1998056354A2/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A61K9/5047—Cellulose ethers containing no ester groups, 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Definitions

  • the invention relates to orally administrable, stable multiple unit prolonged release dosage forms or. Controlled release preparations and methods for making them using a selected polymer.
  • Oral sustained release preparations or dosage forms release the drug F at a predetermined rate and maintain the desired plasma concentration for a longer period than conventional immediate release dosage forms.
  • the patient does not have to take the prolonged-release dosage form as often as the conventional instant or rapid release dosage forms. This in turn improves patient compliance.
  • Matrix tablets containing polymers are already known as a slow-release dose type.
  • the polymers used for retardation purposes can be either hydrophilic or hydrophobic or a mixture thereof.
  • Hydrophilic matrix tablets have recently become very popular because the hydrophilic polymers offer obvious advantages: they are relatively cheap, comparatively non-toxic and can be processed on conventional systems. Matrix tablets are usually available in single unit dosage forms.
  • Tract are less susceptible. They also distribute themselves more uniformly in the gastrointestinal tract and enable more even absorption of the drug. As a result, the inter- and intra-individual fluctuations in the pharmacokinetic profiles are reduced compared to those of the single-unit dosage forms.
  • the multiple unit dosage forms are usually hard gelatin capsules that contain coated pellets, granules, mini tablets or pearls. The rate of release of the active ingredient is often determined by the thickness and type of coating.
  • the previously used multiple unit dose Form applied technology is complicated, requires the use of organic solvents and is expensive compared to single unit dosage forms.
  • the subject of the present invention combines the advantages of multiple unit dosage forms in terms of their behavior in the gastrointestinal tract, e.g. the uniform absorption of the active ingredient and the technological advantages of single unit dosage forms through the inexpensive and simple production of mini matrices.
  • the dose of active substance can be easily adapted to the respective medical needs by varying the number of extrudates.
  • extrudates of different active substances can be filled into the capsule and thus mixtures of active substances can be conveniently brought to the administration.
  • the extrudates can be pressed into tablets using conventional auxiliaries. These tablets disintegrate into the extrudates quickly after administration so that the tablet behaves like a multiple unit dosage form.
  • the easily accessible, inexpensive and non-toxic cellulose ether hydroxypropyl cellulose is preferably chosen.
  • a melt extrusion method is preferably chosen for HPC. This method is simple and economical because it does not require organic solvents. The principle of melt extrusion has been known for over 3 decades (Beckmann 1964).
  • the amount of the water-insoluble polymer should be at least 6% by weight.
  • the desired release rate was achieved by using a mixture of at least two water-soluble polymers with low (1 - 500 cP) and high (1000 - 120,000 cP) viscosity.
  • WO 96 11 674-A1 describes a process according to which a mixture of medicinal substance, HPC and suitable auxiliaries for thermoforming and for modifying the release rate of the medicinal substance is heated, compressed and then injection molded under pressure, which results in a product with a defined shape . Mixtures of HPC with different molecular weights are used to optimize the release.
  • the excipient-drug ratio is increased and the finished product becomes very bulky and also expensive.
  • the product with a defined shape can only be obtained in a single step after complicated manufacturing methods with specially prepared machines.
  • the release rate decreases with time, indicating a reduced stability.
  • melt extrudates with a desired linear release profile and high stability can be obtained in a simple manner.
  • This much simpler process only requires a conventional extruder and does not require any complicated manufacturing methods.
  • the object of the invention is to provide orally administrable, non-porous, stable multiple-unit prolonged-release dosage forms with controlled release, in particular dosage forms which contain only a selected polymer in addition to the active ingredient.
  • Another object of the invention is to provide a method using a single selected polymer to make the above dosage form type. If desired, the extrudates obtained can subsequently be rounded and varnished.
  • the present invention also relates to a process for the production of non-porous multiple unit prolonged-release dosage forms, comprising at least one therapeutically active substance and a hydrophilic thermoplastic but pharmaceutically acceptable polymer and optionally other customary pharmaceutical auxiliaries which, however, do not contribute to the prolonged-release effect.
  • the therapeutically active drug and the polymer are conveyed either simultaneously, without prior mixing, or as a mixture, after prior mixing, in a normal extruder which has previously been heated to a temperature at which the polymer softens and the drug does not degrade.
  • the temperature range at the outlet nozzle of the extruder is 50 to 200 ° C, preferably 80 to 180 ° C, and in particular 110 to 160 ° C.
  • the temperature is 25 ° C., preferably 40 to 70 ° C., preferably 40 to 60 ° C., particularly preferably 50 to 60 ° C.:
  • the temperature in the intermediate area of the extruder lies between the temperature in the product entry area of the extruder and the temperature at the exit nozzle of the extruder.
  • the homogeneous mixture softens during the passage through the extruder and is finally pressed through a plate which contains at least one nozzle with a defined diameter of 0.5 to 3.5 mm, preferably 0.8 to 3.0 mm.
  • the extruded strands which are still soft on leaving the extruder die and quickly become solid at room temperature, are cut into cylinders with a length of 0.5 to 4 mm, preferably 1.0 to 3 mm, immediately after they exit.
  • the extruded strands are granulated immediately (e.g. water-ring granulation or underwater granulation) or cut into pieces immediately (on-line).
  • the extrudates obtained can be filled directly into hard gelatin capsules or, if necessary, rounded beforehand to improve their flow properties.
  • coated extrudates can be coated with conventional auxiliary materials (e.g. micro-
  • the active ingredient can be any orally administered pharmaceuticals, such as anti-infectives, circulatory agents, antifungals, antidepressants, anti-dementics, anti-epileptics, anti-inflammatory drugs, analgesics, anti-asthmatics, anti-thrombotic agents, anti-tumor agents, anti-malarial drugs, non-steroidal anti-inflammatory drugs, anti-inflammatory drugs. Diuretics, antiarrhythmics, hypoglycemic agents, ACE
  • Inhibitors sedatives, decongestants, antihistamines, lipid-lowering agents.
  • drugs are incorporated which do not decompose under the temperatures and processing conditions.
  • the drugs specified in the examples are dihydropyridines.
  • the amount of active ingredient to be administered per dose unit can be varied within wide limits depending on the type of drug and the rate of release. It has proven to be advantageous to use 0.5 to 10 parts by weight, preferably 1 to 5 parts by weight, of the gel-forming polymer per part by weight of active ingredient.
  • Hydroxypropyl cellulose is the preferred polymer for retardation.
  • the molecular weight of the polymer and its degree of substitution play an important role.
  • HPC is preferably used, with an average molecular weight of approximately 100,000 to 1,000,000, in particular approximately 300,000 to 1,000,000.
  • the degree of substitution should be at least 3. If the drug is temperature sensitive, the use of low molecular weight HPC is recommended.
  • the desired release rate is obtained either by selecting a suitable type of polymer and / or by varying the production parameters.
  • the drug release rate is e.g. influenced by the drug concentration in the end product or by process parameters of the extrusion, such as the screw geometry, the extrusion rate, the extrusion temperature, the diameter and the surface of the extrudate, the viscosity of the polymer, etc.
  • auxiliaries which are customary in the manufacture of solid dosage forms in pharmacy and from which Literature are known.
  • none of these auxiliaries is necessary in order to significantly influence the delay in the release of the pharmaceutical substance desired according to the invention. Rather, these auxiliaries only serve to make the process more flexible.
  • the extrudates are lacquered e.g. with pH-independent aqueous dispersions such as an ethyl cellulose dispersion (e.g. Aquacoat EC 30 Trademark of FMC) or a polyacrylate derivative (e.g. Eudragit NE 30 D Trademark of Röhm Pharma).
  • pH-independent aqueous dispersions such as an ethyl cellulose dispersion (e.g. Aquacoat EC 30 Trademark of FMC) or a polyacrylate derivative (e.g. Eudragit NE 30 D Trademark of Röhm Pharma).
  • pore formers such as low-viscosity hydroxypropylmethyl cellulose (HPMC), low-viscosity HPC or low-viscosity hydroxyethyl cellulose, etc.
  • HPMC low-viscosity hydroxypropylmethyl cellulose
  • HPC low-viscosity HPC
  • low-viscosity hydroxyethyl cellulose etc.
  • the varnish has essentially no effect on the release rate, except that there may be a delay in the onset of release during the first two hours after administration (lag time).
  • Typical varnish suspensions are:
  • the lacquer suspensions for example, are produced by first dissolving HPMC and the plasticizer separately in water and then using the dispersion of the film former mixes. In the presence of magnesium stearate, it is dispersed in the aqueous solution of HPMC and plasticizer before the addition of the Eudragit NE 30-D dispersion.
  • Extruded die temperature 150 ° C.
  • the temperature of the various subunits in the extruder barrel is set to a temperature which is at least about 10 ° C below the die temperature.
  • the extrudate is cut into approximately 2 mm long cylinders and painted in a fluidized bed coating system. 0.6 kg of lacquer suspension A is sprayed on per kg of extrudate. The painting is carried out under normal conditions.
  • Example 2 Analogous to Example 1, but the extruded strands were first cut into approximately 4 mm long cylinders.
  • Example 13 Analogous to Example 1, but nisoldipine is used as the drug.
  • Example 13 Analogous to Example 1, but nisoldipine is used as the drug.
  • Example 2 Analogously to Example 1, but nimodipine is used as the drug, low-viscosity HPC (MW 150,000) is used, and the nozzle temperature is 110 ° C.
  • Example 2 The same composition as in Example 1 is in a commercially available extrusion and granulation device (Leistritz) under the same
  • Example 2 The same composition as in Example 1 is extruded under the same extrusion conditions in a commercially available extrusion and granulation device (company Gala) and then immediately granulated and dried by underwater granulation. The resulting extrudates were slightly rounded and therefore easier to process.
  • Example 2 The same composition as in Example 1 is extruded through an extruder with outlet nozzles with a diameter of 1 mm, the extruded strand is cooled by spraying with water and immediately granulated and dried. The extrudates obtained are processed as described in Example 1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des formes galéniques ou des préparations à doses retard à unités multiples, à libération contrôlée et des procédés permettant de les préparer à l'aide d'un polymère sélectionné.
PCT/EP1998/003103 1997-06-09 1998-05-27 Preparations retard a unites multiples et procedes permettant de les preparer Ceased WO1998056354A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU84349/98A AU8434998A (en) 1997-06-09 1998-05-27 Multiple-unit delayed dosage preparations and method for producing the same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19724181.6 1997-06-09
DE1997124181 DE19724181A1 (de) 1997-06-09 1997-06-09 Multiple-unit-retard-Zubereitungen und Verfahren zu ihrer Herstellung

Publications (1)

Publication Number Publication Date
WO1998056354A2 true WO1998056354A2 (fr) 1998-12-17

Family

ID=7831871

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/003103 Ceased WO1998056354A2 (fr) 1997-06-09 1998-05-27 Preparations retard a unites multiples et procedes permettant de les preparer

Country Status (3)

Country Link
AU (1) AU8434998A (fr)
DE (1) DE19724181A1 (fr)
WO (1) WO1998056354A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8834925B2 (en) 2006-08-25 2014-09-16 Purdue Pharma L.P. Tamper resistant dosage forms

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2340812A1 (fr) * 2009-12-18 2011-07-06 Ferring International Center S.A. Granules pour préparations pharmaceutiques, procédés et appareil pour leur production

Cited By (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8834925B2 (en) 2006-08-25 2014-09-16 Purdue Pharma L.P. Tamper resistant dosage forms
US8846086B2 (en) 2006-08-25 2014-09-30 Purdue Pharma L.P. Tamper resistant dosage forms
US8894988B2 (en) 2006-08-25 2014-11-25 Purdue Pharma L.P. Tamper resistant dosage forms
US8894987B2 (en) 2006-08-25 2014-11-25 William H. McKenna Tamper resistant dosage forms
US8911719B2 (en) 2006-08-25 2014-12-16 Purdue Pharma Lp Tamper resistant dosage forms
US9084816B2 (en) 2006-08-25 2015-07-21 Purdue Pharma L.P. Tamper resistant dosage forms
US9095614B2 (en) 2006-08-25 2015-08-04 Purdue Pharma L.P. Tamper resistant dosage forms
US9095615B2 (en) 2006-08-25 2015-08-04 Purdue Pharma L.P. Tamper resistant dosage forms
US9101661B2 (en) 2006-08-25 2015-08-11 Purdue Pharma L.P. Tamper resistant dosage forms
US9486413B2 (en) 2006-08-25 2016-11-08 Purdue Pharma L.P. Tamper resistant dosage forms
US9486412B2 (en) 2006-08-25 2016-11-08 Purdue Pharma L.P. Tamper resistant dosage forms
US9492393B2 (en) 2006-08-25 2016-11-15 Purdue Pharma L.P. Tamper resistant dosage forms
US9492390B2 (en) 2006-08-25 2016-11-15 Purdue Pharma L.P. Tamper resistant dosage forms
US9492391B2 (en) 2006-08-25 2016-11-15 Purdue Pharma L.P. Tamper resistant dosage forms
US9492392B2 (en) 2006-08-25 2016-11-15 Purdue Pharma L.P. Tamper resistant dosage forms
US9492389B2 (en) 2006-08-25 2016-11-15 Purdue Pharma L.P. Tamper resistant dosage forms
US9545380B2 (en) 2006-08-25 2017-01-17 Purdue Pharma L.P. Tamper resistant dosage forms
US9763933B2 (en) 2006-08-25 2017-09-19 Purdue Pharma L.P. Tamper resistant dosage forms
US9763886B2 (en) 2006-08-25 2017-09-19 Purdue Pharma L.P. Tamper resistant dosage forms
US9770417B2 (en) 2006-08-25 2017-09-26 Purdue Pharma L.P. Tamper resistant dosage forms
US9770416B2 (en) 2006-08-25 2017-09-26 Purdue Pharma L.P. Tamper resistant dosage forms
US9775808B2 (en) 2006-08-25 2017-10-03 Purdue Pharma L.P. Tamper resistant dosage forms
US9775812B2 (en) 2006-08-25 2017-10-03 Purdue Pharma L.P. Tamper resistant dosage forms
US9775809B2 (en) 2006-08-25 2017-10-03 Purdue Pharma L.P. Tamper resistant dosage forms
US9775811B2 (en) 2006-08-25 2017-10-03 Purdue Pharma L.P. Tamper resistant dosage forms
US9775810B2 (en) 2006-08-25 2017-10-03 Purdue Pharma L.P. Tamper resistant dosage forms
US10076498B2 (en) 2006-08-25 2018-09-18 Purdue Pharma L.P. Tamper resistant dosage forms
US10076499B2 (en) 2006-08-25 2018-09-18 Purdue Pharma L.P. Tamper resistant dosage forms
US11298322B2 (en) 2006-08-25 2022-04-12 Purdue Pharma L.P. Tamper resistant dosage forms
US11304908B2 (en) 2006-08-25 2022-04-19 Purdue Pharma L.P. Tamper resistant dosage forms
US11304909B2 (en) 2006-08-25 2022-04-19 Purdue Pharma L.P. Tamper resistant dosage forms
US11826472B2 (en) 2006-08-25 2023-11-28 Purdue Pharma L.P. Tamper resistant dosage forms
US11904055B2 (en) 2006-08-25 2024-02-20 Purdue Pharma L.P. Tamper resistant dosage forms
US11938225B2 (en) 2006-08-25 2024-03-26 Purdue Pharm L.P. Tamper resistant dosage forms
US11964056B1 (en) 2006-08-25 2024-04-23 Purdue Pharma L.P Tamper resistant dosage forms
US12246094B2 (en) 2006-08-25 2025-03-11 Purdue Pharma L.P. Tamper resistant dosage forms
US12280152B2 (en) 2006-08-25 2025-04-22 Purdue Pharma L.P. Tamper resistant dosage forms
US12396955B2 (en) 2006-08-25 2025-08-26 Purdue Pharma L.P. Tamper resistant dosage forms

Also Published As

Publication number Publication date
DE19724181A1 (de) 1998-12-10
AU8434998A (en) 1998-12-30

Similar Documents

Publication Publication Date Title
EP1113787B1 (fr) Preparations pharmaceutiques a liberation controlee en fonction de l'agitation et leur procede de production
DE3587274T2 (de) Dosierungsform eine vielzahl mit einer diffusionshuelle ueberzogener einheiten enthaltend.
DE69230028T3 (de) Methode um eine stabilisierte Formulierung mit kontrollierter Abgabe mit einem Acrylpolymerüberzug zu erhalten
DE19927688A1 (de) Mehrschichttablette zur Verabreichung einer fixen Kombination von Tramadol und Diclofenac
EP0864325A2 (fr) Préparation pharmaceutique solide d'au moins deux phases d'un opioide analgésique à libération retardée
DE1617724A1 (de) Verfahren zur Herstellung von Arzneimitteln mit verzoegerter Wirkung
DE19961897A1 (de) Verwendung eines Filmüberzuges als geschmacksmaskierendes Coating von pharmazeutischen Darreichungsformen
WO2006072367A1 (fr) Produits pharmaceutiques solides, administres par voie orale et contenant du rivaroxaban, a liberation modifiee
EP1143936A2 (fr) FORMULATIONS DE MEDICAMENTS CONTENANT UN OPIOIDE ET UN $g(a)-AGONISTE
DE69526467T2 (de) Arzneizubereitungen für die verlängerte Trimetazidinfreisetzung nach oraler Verabreichnung
DE19733505A1 (de) Schnell wirksames Analgeticum
EP0596203A1 (fr) Préparations sous forme de particules solides contenant des principes actifs et des polymères hydrosolubles
CH705273B1 (de) Pharmazeutische Zusammensetzung – umfassend Hydromorphon und Naloxon.
EP0615442B1 (fr) Matrice thermocollo dale reglee par des sols a base de gelatine utile dans des formes d'administration perorale a action prolongee
DE60126332T2 (de) Wärmeformbare feste pharmazeutische zusammensetzung für die kontrollierte freigabe von ivabradin
DE10031043A1 (de) Retardzubereitungen von Chinolonantibiotika und Verfahren zu ihrer Herstellung
CH634748A5 (de) Ueberzugsmaterial zur geregelten wirkstoffabgabe von arzneimitteln sowie verfahren zu dessen herstellung.
DE602004006443T2 (de) Beschichtete minitabletten von venlafaxinhydrochlorid mit verlängerter freisetzung
DE60307819T2 (de) Venlafaxine Hydrochloridformulierungen mit verzögerter Freisetzung
EP1487422B1 (fr) Films de revetement a liberation tres controlee et a grande stabilite
EP1480623A1 (fr) Medicament contenant des principes actifs reduisant le taux de cholesterol, a liberation prolongee du principe actif
EP0691843B1 (fr) Micro-comprime retard de derives de beta-phenylpropiophenone
DE10215131A1 (de) Matrix zur verzögerten, gleichbleibenden und unabhängigen Freisetzung von Wirkstoffen
EP1202715B1 (fr) Extrudats a liberation rapide, leur procede de production et preparations pouvant etre obtenues partir desdits extrudats
EP1795186A2 (fr) Formulation medicamenteuse contenant flupiritin à libération contolée du principe actif

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM GW HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

NENP Non-entry into the national phase

Ref country code: CA

NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 1999501424

Format of ref document f/p: F

122 Ep: pct application non-entry in european phase