EP2192894A2 - Neuartiges verfahren zur herstellung trockener und wasserdispersibler pharmazeutischer formen - Google Patents

Neuartiges verfahren zur herstellung trockener und wasserdispersibler pharmazeutischer formen

Info

Publication number
EP2192894A2
EP2192894A2 EP08827662A EP08827662A EP2192894A2 EP 2192894 A2 EP2192894 A2 EP 2192894A2 EP 08827662 A EP08827662 A EP 08827662A EP 08827662 A EP08827662 A EP 08827662A EP 2192894 A2 EP2192894 A2 EP 2192894A2
Authority
EP
European Patent Office
Prior art keywords
polyoxyethylene
active ingredient
dispersed
microcrystalline cellulose
fatty acid
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.)
Withdrawn
Application number
EP08827662A
Other languages
English (en)
French (fr)
Inventor
Patrice Binay
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.)
BIONETWORK
Original Assignee
Coretecholding
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 Coretecholding filed Critical Coretecholding
Publication of EP2192894A2 publication Critical patent/EP2192894A2/de
Withdrawn legal-status Critical Current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
    • A61K9/14—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
    • A61K9/1617—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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats

Definitions

  • the drugs have low solubility in water or are poorly salifiable during passage into the stomach, so that they are only partially resorbed.
  • Previous literature has indicated that digestive resorption can be favorably modified by the study of particle size, by the addition of nonionic surfactants in particular, as well as by the addition of a solubilizing agent.
  • micronization of the active ingredient adequately increases the external surface area of the powdery product and is already an approach to this problem.
  • micronization is only appropriate for certain pharmaceutical forms, such as dispersions, or as a filler in capsules. It can not be a general solution for this problem of resorption because some active ingredients are difficult to micronize since too fusible or having a too fragile chemical structure.
  • surfactants can increase the solubility of certain active ingredients and thereby improve the resorption kinetics, but this does not systematically result in higher blood levels.
  • This improvement in the passage through the digestive tract seems to be the result of a decrease in surface tension involving an increase in the permeability of the digestive mucosa. Nevertheless, these large amounts of surfactants are often accompanied by a laxative effect that does not contribute to good absorption.
  • This vitreous state is not very orderly and easy to break. It contributes significantly to an increase in the dissolution rate, especially for substances that are poorly soluble in aqueous media.
  • this technique has had limited development because of the difficulty in generalizing it. In some cases, the dissolution rate is large. In other cases, the dissolution rate is lower and tends to reach an asymptotic value.
  • Another approach to this problem has been the production of solid dispersions of a therapeutic agent in a hydrophilic vehicle having increased solubility in the aqueous medium.
  • This approach consists, first of all, in dissolving the therapeutic active ingredient in a very volatile organic solvent, in which a very hydrophilic polymer such as polyvinylpyrrolidone has been added. Then, the solvent is evaporated to dryness to form a co-precipitate of therapeutic agent and hydrophilic polymer.
  • This technique has made it possible to obtain a marked improvement in absorption kinetics, but it is not suitable for any type of active ingredient.
  • this technique often requires the addition to the solution of a surfactant which increases the wetting ability by the digestive media and possibly limits the phenomenon of crystal formation occurring during the conservation of solid dispersions.
  • the formation of crystalline products contributes to a decrease in the dissolution rate in time function (see Kigudin et al Chem Pharma Bull 9 (1961) 866-872, Duchene D. Pharma 1 (11) (1985) 1064-1073).
  • this technique requires the formation of co-precipitates in a very hydrophilic lactam, such as polyvinylpyrrolidone, having a molecular weight ranging from 10,000 to 5,000, and an oxygenated or chlorinated solvent or mixtures thereof (see patent US-5776495).
  • a very hydrophilic lactam such as polyvinylpyrrolidone, having a molecular weight ranging from 10,000 to 5,000, and an oxygenated or chlorinated solvent or mixtures thereof (see patent US-5776495).
  • the solvent described herein is a vehicle which can be hydrophobic or hydrophilic, which is miscible with water and has a melting point of less than 250 ° C.
  • the preferred solvent is polyethylene glycol with or without Poloxamer 188.
  • Polyethylene stearate 32 is not mentioned in this document and the inert material necessary for the spraying of the vehicle is not micro-crystalline cellulose but lactose.
  • the present invention provides a much simpler and much more satisfactory solution to the problem of the dissolution and intestinal resorption of active ingredients with little or no water-soluble or non-salifiable in the gastric juice.
  • the process according to the invention consists in producing a dispersion of one or more active principle (s) in a polyoxyethylene fatty acid ester 32 easily fusible. This dispersion is sprayed on a granular excipient in a fluidized bed. The powder mixture thus formed is dispensed into pharmaceutical compositions after optional dilution with a pharmaceutically acceptable non-toxic inert carrier.
  • active principle s
  • the expression “easily fuse” here means that this ester melts below 80 0 C and more particularly between 40 and 50 0 C.
  • the polyoxyethylene 32 fatty acid ester used is a polyoxyethylene 32 distearate which melts at around 50 ° C. to 60 ° C.
  • Polyoxyethylene distearate 32 is a product of the invention. commercially available. A product belonging to the same family is sold under the brand Kessco ® PEG 1540 DS (Stepan).
  • the granular excipient is an inert material such as cellulose, dextran, colloidal silica, vinylpyrrolidone polymers or copolymers, polyvinylpyrrolidones, acrylic polymers such as polycarbophil and similar products .
  • a preferred granular material is micro-crystalline cellulose and preferably the pharmaceutical quality marketed under the name AVICEL PH and in particular the quality sold under the name AVICEL PH 105.
  • the content of active ingredient dispersed in the polyoxyethylene fatty acid ester 32 may vary in large proportions because these esters are very good solvents. It is possible to perform both dilute solutions and concentrated solutions.
  • a preferred concentration of active ingredient varies from 30 to 50% of active ingredient in the fatty acid ester. Such contents allow easy entry into solution.
  • a preferred concentration is that consisting of 40 to 50% of active ingredient.
  • compositions according to the invention mention may in particular be made of:
  • Nifedipine and analogues (Nitrendipine, Nisoldipine ).
  • analgesics Fentanyl, Dextropropoxyphene, Sufentanyl.
  • opiate derivatives Nalbuphine, Naltrexone, Dihydrocodeinone, Buprenorphine, or Methadone.
  • the invention finds particular use for the production of pharmaceutical forms whose bioavailability is greatly improved and whose active ingredient is an antilipemic agent and / or cholesterol-lowering agents. More specifically, the preparations based on derivatives of clofibric acid or fenofibric acid such as clofibrate, fenofibrate, gemfibrozil, bezafibrate, ciprofibrate, pirifibrate or simfibrate.
  • HMG coA reductase inhibitors such as Atorvastatin, Cerivastatin, Fluvastatin, Pravastatin and its sodium salt or Simvastatin, or triptans such as Sumatriptan or Frovatriptan.
  • the advantage of a solvent such as a polyoxyethylene fatty acid ester 32 lies in the fact that this product is not likely to promote or produce a transesterification or to increase the toxicity of the active ingredient.
  • Another peculiarity of the present invention is to be able to produce bioavailable forms of hormonal products which are not or hardly absorbable in the digestive tract, such as progesterone, androsterone, chlormadinone acetate or Melengestrol.
  • the alkylated derivatives are used in the 17 ⁇ or 6 ⁇ position to obtain digestive-active compounds (cyproterone, demegestone, promegestone, norethynodiol acetate, ethynyl estradiol).
  • This substitution has the disadvantage of inducing annoying side effects (androgenic or anti-androgenic action, anti-estrogenic action and especially hepatotoxic effects) which are to be avoided in particular.
  • natural progesterone or its derivatives dihydroprogesterone, 17 ⁇ -hydroxyprogesterone
  • the dispersions according to the invention allow the production of pharmaceutical compositions containing, in addition to the active ingredient dispersed on the inert support, one or more pharmaceutically acceptable non-toxic inert excipients.
  • the content of active ingredient is calculated so that the final pharmaceutical formulation contains an effective and non-toxic active ingredient content.
  • the amount of excipient is calculated so that the concentration of active fraction is of the order of 50%, that is to say, it does not exceed 50% and is preferably between 20 and 40%.
  • a particular example is the preparation of pharmaceutical compositions based on fenofibrate absorbate in microcrystalline cellulose.
  • the active ingredient content ranges from 50 to 150 mg per unit dose and preferably 60 mg, 90 mg or 130 mg of fenofibrate.
  • the microcrystalline cellulose content varies from 40 to 60 mg per unit dose.
  • compositions whose active ingredient content ranges from 5 to 50 mg and in particular from 25 to 40 mg per unit dose.
  • the content of polyoxyethylene distearate 32 will also be 5 to 100 mg per unit dose and the excipient content will also be between 5 and 100 mg.
  • Fenofibrate, progesterone or amiodarone preparations are provided hereinafter by way of example. They do not limit the invention.
  • the present invention also relates to the production of sublingual forms or oral tablets. They are intended to be placed under the tongue for sublingual tablets or glued to the palate for oral tablets. These types of tablets made according to the process of the invention show an even greater bioavailability.
  • sublingual or oral tablets are made by the process according to the invention but the granular powdery product is then tabletted by adding a binding agent, a compressing agent and a slip agent.
  • Figures 1 to 4 show the results of pharmacokinetic studies carried out with compositions according to the invention for different active ingredients.
  • the minimum efficiency concentration (MEC) is indicated for each of the compounds.
  • the terms “formulation” and “preparation” are equivalent to the term “composition”.
  • FIG. 1 is a graph showing the average blood concentration (in ⁇ g / ml) as a function of the resorption time after ingestion of the paracetamol tablets (in hours).
  • the results are obtained with a preparation based on 0.350 g of paracetamol produced according to the method of the invention. These results are compared with those obtained with commercial tablets containing the same dosage of paracetamol.
  • FIG. 2 is a graph showing the blood concentration (in ⁇ g / ml) as a function of the resorption time after administration of indomethacin (in hours). This figure represents the results obtained with a formulation prepared according to the method of the invention, and whose active ingredient is indomethacin, in comparison with the results obtained with a commercial formulation of indomethacin.
  • the peak blood concentration for the formulation according to the invention appears rapidly since only 1 hour after the administration of indomethacin.
  • the maximum concentration (Cmax) observed during this peak is 6 ⁇ g / mL for the formulation according to the invention.
  • Cmax the maximum concentration observed during this peak
  • the maximum concentration (C'max) of the commercial formulation is then less than 4 ⁇ g / ml.
  • the EMC of indomethacin is reached 3 hours after the administration of the formulation according to the invention whereas this concentration is never reached for the commercial formulation.
  • FIG. 3 is a graph showing the blood concentration (in ⁇ g / ml) as a function of the resorption time after administration of sumatriptan (in hours). The curves represent the results obtained with a composition according to the invention whose active ingredient is sumatriptan in comparison with those obtained with the commercial product.
  • FIG. 4 is a graph showing the plasma concentration (in ⁇ g / ml) as a function of the resorption time after oral administration of frovatriptan (in hours). The results are obtained from a preparation according to the invention, the active ingredient of which is frovatriptan. These results are compared with those obtained with the commercial formulation of this drug.
  • compositions according to the invention show that in the case of the compositions according to the invention, the active ingredients are reabsorbed more quickly by the body and in greater quantities. Indeed, the resorption of the active ingredients is technically facilitated by the compositions according to the invention and the Cmax concentrations obtained with the compositions according to the invention much higher than the C'max obtained with the similar products of commerce.
  • EMFs are never achieved with the commercial compositions.
  • the EMFs are reached for each of the active ingredients presented in these examples.
  • these concentrations are reached at most about 3 hours after administration of the compositions according to the invention.
  • the compositions according to the invention allow not only a faster resorption but also to reach the concentrations of efficiencies in a short time in cases where these concentrations are not reached with the commercial compositions.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
EP08827662A 2007-07-06 2008-07-07 Neuartiges verfahren zur herstellung trockener und wasserdispersibler pharmazeutischer formen Withdrawn EP2192894A2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0704874A FR2918277B1 (fr) 2007-07-06 2007-07-06 Nouveau procede de production de formes pharmaceutiques seches hydrodispersibles et les compositions hydrodispersibles ainsi obtenues
PCT/FR2008/000973 WO2009024686A2 (fr) 2007-07-06 2008-07-07 Procede de production de formes pharmaceutiques seches hydrodispersibles

Publications (1)

Publication Number Publication Date
EP2192894A2 true EP2192894A2 (de) 2010-06-09

Family

ID=39469562

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08827662A Withdrawn EP2192894A2 (de) 2007-07-06 2008-07-07 Neuartiges verfahren zur herstellung trockener und wasserdispersibler pharmazeutischer formen

Country Status (9)

Country Link
US (1) US20130064897A1 (de)
EP (1) EP2192894A2 (de)
JP (1) JP5560188B2 (de)
KR (1) KR20100038188A (de)
BR (1) BRPI0814027A2 (de)
CA (1) CA2694059A1 (de)
FR (1) FR2918277B1 (de)
RU (1) RU2497502C2 (de)
WO (1) WO2009024686A2 (de)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9301920B2 (en) 2012-06-18 2016-04-05 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
EP2782584B1 (de) 2011-11-23 2021-06-09 TherapeuticsMD, Inc. Natürliche kombinierte hormonersatzformulierungen und -therapien
US10806697B2 (en) 2012-12-21 2020-10-20 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US20150196640A1 (en) 2012-06-18 2015-07-16 Therapeuticsmd, Inc. Progesterone formulations having a desirable pk profile
US10806740B2 (en) 2012-06-18 2020-10-20 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US20130338122A1 (en) 2012-06-18 2013-12-19 Therapeuticsmd, Inc. Transdermal hormone replacement therapies
US11266661B2 (en) 2012-12-21 2022-03-08 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10471072B2 (en) 2012-12-21 2019-11-12 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US9180091B2 (en) 2012-12-21 2015-11-10 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
US10568891B2 (en) 2012-12-21 2020-02-25 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10537581B2 (en) 2012-12-21 2020-01-21 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11246875B2 (en) 2012-12-21 2022-02-15 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
AR100562A1 (es) 2014-05-22 2016-10-12 Therapeuticsmd Inc Composición farmacéutica de estradiol y progesterona para terapia de reemplazo hormonal
US10328087B2 (en) 2015-07-23 2019-06-25 Therapeuticsmd, Inc. Formulations for solubilizing hormones
KR20180126582A (ko) 2016-04-01 2018-11-27 쎄러퓨틱스엠디, 인코퍼레이티드 스테로이드 호르몬 약제학적 조성물
WO2017173044A1 (en) 2016-04-01 2017-10-05 Therapeuticsmd Inc. Steroid hormone compositions in medium chain oils

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE9003296L (sv) * 1990-10-16 1992-04-17 Kabi Pharmacia Ab Foerfarande foer att formulera laekemedel
FR2722984B1 (fr) 1994-07-26 1996-10-18 Effik Lab Procede de preparation de formes pharmaceutiques seches et les compositions pharmaceutiques ainsi realisees
US6248363B1 (en) * 1999-11-23 2001-06-19 Lipocine, Inc. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
US20030180352A1 (en) * 1999-11-23 2003-09-25 Patel Mahesh V. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
EP1239844B1 (de) * 1999-12-20 2005-06-08 Nicholas J. Kerkhof Verfahren zur herstellung von nanometer partikeln durch fliessbett- sprühtrocknung
DE10244681A1 (de) * 2002-09-24 2004-04-08 Boehringer Ingelheim International Gmbh Neue feste Telmisartan enthaltende pharmazeutische Formulierungen und deren Herstellung
US20040185170A1 (en) * 2003-03-21 2004-09-23 Shubha Chungi Method for coating drug-containing particles and formulations and dosage units formed therefrom
KR20060085686A (ko) 2003-10-10 2006-07-27 라이프사이클 파마 에이/에스 피브레이트를 포함하는 고형 제제
US20050181049A1 (en) * 2003-11-19 2005-08-18 Dong Liang C. Composition and method for enhancing bioavailability
KR100629771B1 (ko) * 2004-01-27 2006-09-28 씨제이 주식회사 결정성이 감소되거나 무정형화된 올티프라즈의 제조방법
US7635745B2 (en) * 2006-01-31 2009-12-22 Eastman Chemical Company Sulfopolyester recovery

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2009024686A2 *

Also Published As

Publication number Publication date
JP2010532336A (ja) 2010-10-07
US20130064897A1 (en) 2013-03-14
BRPI0814027A2 (pt) 2015-02-03
WO2009024686A3 (fr) 2009-04-23
RU2497502C2 (ru) 2013-11-10
FR2918277B1 (fr) 2012-10-05
RU2010103999A (ru) 2011-08-20
CA2694059A1 (fr) 2009-02-26
JP5560188B2 (ja) 2014-07-23
KR20100038188A (ko) 2010-04-13
WO2009024686A2 (fr) 2009-02-26
FR2918277A1 (fr) 2009-01-09

Similar Documents

Publication Publication Date Title
WO2009024686A2 (fr) Procede de production de formes pharmaceutiques seches hydrodispersibles
EP0757911B1 (de) Fenofibrathaltige neue galenische Arzneizusammensetzungen und ihre Verwendung
EP1313453B1 (de) Träger in partikelform zur verbesserung der oral- absorption von wikstoffen
JP7437074B2 (ja) リバスチグミンを含む長期持続型製剤およびその製造方法
WO1997004749A1 (fr) Procede de preparation de formes pharmaceutiques seches et les compositions pharmaceutiques ainsi realisees
US20110086070A1 (en) Orally disintegrating compositions of rhein or diacerein
US10314801B2 (en) Taste-masked oral pharmaceutical composition
EP1189602A1 (de) Morphinsulfat enthaltende mikrogranulate, verfahren zu deren herstellung und pharmazeutische zusammensetzungen
EP2323627A1 (de) Neue schnell wirkende pharmazeutische formen und verwendungen der daraus resultierenden pharmazeutischen zusammensetzungen
EP0117164B1 (de) Arzneimittel mit programmierter Abgabe, assoziierend Acetylsalicylsäure mit Dihydroergotamine
CN116098872A (zh) 一种注射用阿哌沙班长效微球及其制备方法
KR100956583B1 (ko) 유비데카레논의 고체분산체와 그 제조방법 및 이를포함하는 약제학적 조성물
JP2008534584A (ja) フェノフィブラート含有メントール又はｐｅｇ／ポロキサマー混合物の改良製剤
JP2009522258A (ja) 増大したバイオアベイラビリティを有するフェノフィブラートの医薬製剤
ZA200605290B (en) Pharmaceutical compositions comprising lercanidipine
JP2935117B2 (ja) ナノスフェア製剤
FR2803748A1 (fr) Composition d'itraconazole et procede de preparation
CA2182024C (fr) Procede de preparation de formes pharmaceutiques seches et les compositions pharmaceutiques ainsi realisees
CA2187153C (en) Effervescent pharmaceutical formulations containing controlled release biodegradable microcapsules
JP5134818B2 (ja) 脂質制御薬物製剤の製造のための方法
ES2325450T3 (es) Formulaciones farmaceuticas de fenofibrato con una biodisponibilidad mejorada.
WO2013022410A2 (en) Production method for effervescent formulations comprising dexketoprofen
JP2019189552A (ja) 医薬組成物およびその製造方法
FR2832312A1 (fr) Procede de preparation de microparticules sans solvant toxique, microparticules obtenues selon ce procede, utilisations et compositions pharmaceutiques
KR20080087845A (ko) 개선된 생체이용률을 갖는 페노피브레이트의 약학적 제제

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20100406

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA MK RS

17Q First examination report despatched

Effective date: 20100909

DAX Request for extension of the european patent (deleted)
RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: BIONETWORK

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: BIONETWORK

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20151027