FR2494112A1 - - Google Patents

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FR2494112A1
FR2494112A1 FR8024568A FR8024568A FR2494112A1 FR 2494112 A1 FR2494112 A1 FR 2494112A1 FR 8024568 A FR8024568 A FR 8024568A FR 8024568 A FR8024568 A FR 8024568A FR 2494112 A1 FR2494112 A1 FR 2494112A1
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fenofibrate
derivatives
microgranules
weight
new
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FR2494112B1 (en
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Priority to FR8024568A priority Critical patent/FR2494112B1/fr
Priority to BE1/10357A priority patent/BE891129A/en
Priority to PCT/FR1981/000148 priority patent/WO1982001649A1/en
Priority to DE19813152519 priority patent/DE3152519C2/en
Priority to AT0906481A priority patent/AT387517B/en
Priority to NL8120434A priority patent/NL8120434A/en
Priority to EP81903096A priority patent/EP0065531A1/en
Priority to IT25185/81A priority patent/IT1144948B/en
Publication of FR2494112A1 publication Critical patent/FR2494112A1/fr
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    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • 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
    • A61K9/5073—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 having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—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 having two or more different coatings optionally including drug-containing subcoatings with drug-free core

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

Abstract

The medicine is formed with granules, each of them being comprised of a neutral core (saccharose + starch) covered with a first layer of phenofibrate admixed with an excipient, and with a second microporous outer layer of an edible polymer. The daily administration of one capsule of 250 mg instead of three doses of 100 mg allows to reduce the dosing and the number of administrations due to the progressive and retarded release of the phenofibrate. A minimum dose is maintained in the blood, high temporary concentrations are avoided and the total ingested quantity is reduced.

Description

La présente invention concerne une nouvelle forme galénique du FENOFI
URATE (DCI) et/ou ses dérivés, son procédé d'obtention et les médicaments comprenant cette forme.The present invention relates to a new dosage form of FENOFI
URATE (DCI) and / or its derivatives, its production process and the drugs comprising this form.

On sait que le FENOFIBRATE est utilisé pour le traitement des hyperlipidémies, hypercholestérolémies et hypertriglycéridémies endogènes de l'adulte. Ainsi, on peut observer chez l'homme soumis à un traitement par le FENOFIBRATE, à raison de 300 à 400 mg par jour, une réduction de la cholestérolémie de 20 à 25 % et une réduction de la triglycéridémie de 40 à 50 %. FENOFIBRATE is known to be used for the treatment of endogenous hyperlipidemia, hypercholesterolaemia and hypertriglyceridaemia in adults. Thus, in humans subjected to treatment with FENOFIBRATE, at a rate of 300 to 400 mg per day, a reduction in cholesterolemia of 20 to 25% and a reduction in triglyceridemia of 40 to 50% can be observed.

Cette action significative se manifeste dès le premier mois de traitement et persiste après 30 mois de traitement. This significant action manifests itself from the first month of treatment and persists after 30 months of treatment.

En raison de leur fréquence (4 à 5 Z de la population française) et de leur rôle dans la génèse de l'artériosclérose, les hyperlipidémies contribuent à l'augmentation du risque statistique d'accident vasculaire, en particulier coronarien. Because of their frequency (4 to 5% of the French population) and their role in the genesis of arteriosclerosis, hyperlipidemias contribute to the increase in the statistical risk of vascular accident, in particular coronary.

D'une manière générale, le traitement des hyperlipidémies par le FENO
FIBRATE constitue un traitement symptomatique à long terme non dénué de risques.In general, the treatment of hyperlipidemia with FENO
FIBRATE is a long-term symptomatic treatment not without risk.

En particulier, on a pu relever des cas d'atteinte hépatique , de troubles digestifs et intestinaux. In particular, there have been cases of liver damage, digestive and intestinal disorders.

En outre, le risque de lithiase biliaire induit par la prise de FENO
FIBRATE n'est pas à exclure.In addition, the risk of cholelithiasis induced by taking FENO
FIBRATE is not to be excluded.

Usuellement le FENOFIBRATE est présenté sous forme de gélules dosées à 100 mg de principe actif : la posologie journalière moyenne est de 300 à 400 mg, parfois 600 mg. Usually FENOFIBRATE is presented in the form of capsules containing 100 mg of active ingredient: the average daily dosage is 300 to 400 mg, sometimes 600 mg.

La présente invention a pour objet une nouvelle forme galénique à libération programmée retardée de FENOFIBRATE et/ou ses dérivés et est remarquable en ce qu'elle est constituée par des microgranules comprenant une âme neutre constituée d'un grain d'un excipient inerte comprenant au moins deux composants du type appartenant à la classe constituée par le saccharose, l'amidon, le talc, la silice desséchante, le lactose et l'acide stéarique, ce grain neutre est muni d'une première couche comprenant le
FENOFIBRATE et/ou ses dérivés puis d'une seconde couche extérieure constituée par une enveloppe microporeuse comprenant au moins un polymère naturel et/ou synthétique appartenant à la classe constituée par la gomme laque, la gomme arabique, la gélatine, l'éthylcellulose, l'acétophtalate de cellulose, le triacétate de cellulose, le polyoxyéthylèneglycol, les méthacrylates, le copolymère styrène - acrylonitrile et le polyvinyl pyrrolidone en enveloppes successives. The present invention relates to a new dosage form with delayed programmed release of FENOFIBRATE and / or its derivatives and is remarkable in that it is constituted by microgranules comprising a neutral core consisting of a grain of an inert excipient comprising at at least two components of the type belonging to the class consisting of sucrose, starch, talc, drying silica, lactose and stearic acid, this neutral grain is provided with a first layer comprising the
FENOFIBRATE and / or its derivatives then a second outer layer consisting of a microporous envelope comprising at least one natural and / or synthetic polymer belonging to the class consisting of shellac, gum arabic, gelatin, ethylcellulose, l cellulose acetophthalate, cellulose triacetate, polyoxyethylene glycol, methacrylates, styrene-acrylonitrile copolymer and polyvinyl pyrrolidone in successive envelopes.

En particulier, l'enveloppe microporeuse peut être formée de gomme laque selon une proportion en poids variant entre 2 et 10 % et l'excipient inerte peut être un mélange comprenant de 40 à 80 % en poids de saccharose et de 10 à 40 Z en poids d'amidon. In particular, the microporous envelope can be formed of shellac in a proportion by weight varying between 2 and 10% and the inert excipient can be a mixture comprising from 40 to 80% by weight of sucrose and from 10 to 40% by weight. starch weight.

Selon une forme de réalisation de l'invention, la première couche peut comprendre de I à 20 % en poids de FENOFIBRATE et/ou ses dérivés,de 0,01 % à 0,5 % en poids d'acide stéarique, de 5 à 15 % en poids de talc et de 2 à 10 z en poids de silice desséchante. En outre, l'amie neutre peut comprendre des adsorbats de FENOFIBRATE et/ou ses dérivés. According to one embodiment of the invention, the first layer may comprise from I to 20% by weight of FENOFIBRATE and / or its derivatives, from 0.01% to 0.5% by weight of stearic acid, from 5 to 15% by weight of talc and from 2 to 10% by weight of drying silica. In addition, the neutral friend may include adsorbates of FENOFIBRATE and / or its derivatives.

L'invention a également pour objet un procédé d'obtention de la nouvelle forme galénique remarquable en ce qu'on prépare au préalable des microgranules neutres tamisés et séchés, qu'on projette sur ces microgranules une solution dans l'alcool absolu de FENOFIBRATE et/ou ses dérivés, qu'on enrobe ensuite lesdits microgranules pour réaliser la première couche en un ou plusieurs enrobages, puis qu on forme l'enveloppe microporeuse par enrobage à l'aide dudit polymère en solution dans un solvant. The subject of the invention is also a process for obtaining the new galenical form which is remarkable in that neutral sieved and dried microgranules are prepared beforehand, that a solution in absolute alcohol of FENOFIBRATE is projected onto these microgranules and / or its derivatives, which are then coated with said microgranules to produce the first layer in one or more coatings, then the microporous envelope is formed by coating with said polymer in solution in a solvent.

De plus, la présente invention a pour objet des médicaments comprenant la nouvelle forme d'administration du FENOFIBRATE et/ou ses dérivés, sous forme de microgranules actifs mélangés à des micro granules neutres non enrobés afin d'obtenir une concentration prédéterminée en FENOFIBRATE et/ou ses dérivés, cet ensemble de microgranules étant présenté sous forme de gélules, de comprimés, de suppositoires, de sirop, de granulés ou de poudre. In addition, the present invention relates to medicaments comprising the new form of administration of FENOFIBRATE and / or its derivatives, in the form of active microgranules mixed with uncoated neutral micro granules in order to obtain a predetermined concentration of FENOFIBRATE and / or its derivatives, this set of microgranules being presented in the form of capsules, tablets, suppositories, syrup, granules or powder.

L'ensemble des caractéristiques et avantages de l'invention seront mieux compris par l'homme de l'art en se référant à la description qui va suivre de modes de réalisation particuliers pris à titre d'exemples non limitatifs de la nouvelle forme galénique, de son procédé et de ses applications thérapeutiques, en particulier en relation avec les contrôles pharmacologiques et cliniques effectués en utilisant la nouvelle forme galénique. All of the characteristics and advantages of the invention will be better understood by a person skilled in the art by referring to the following description of particular embodiments taken by way of nonlimiting examples of the new galenical form, its process and its therapeutic applications, in particular in relation to the pharmacological and clinical checks carried out using the new galenical form.

EXEMPLE DE PREPARATION DE LA NOUVELLE FORME GALENIQUE
On indique ci-après un exemple de fabrication correspondant à 100 000 gélules dosées à 250 mg.EXAMPLE OF PREPARATION OF THE NEW GALENIC FORM
A manufacturing example corresponding to 100,000 capsules containing 250 mg is indicated below.

1) Formule de fabrication
.FENOFIBRATE ....................................... 25 kg
.Saccharose, amidon, gomme laque, talc, silice dessé
chante, acide stéarique, polyvidone, polymère métha
crylique ........................................ 27,5 kg
.Alcool éthylique absolu .. q s
On granule de l'amidon de mais et du saccharose puis on tamise et on turbine longuement les grains de façon à les rendre parfaitement sphériques.1) Manufacturing formula
.FENOFIBRATE ....................................... 25 kg
. Sucrose, starch, shellac, talc, dried silica
sings, stearic acid, polyvidone, metha polymer
crylic ........................................ 27.5 kg
.Absolute ethyl alcohol .. qs
Granulate corn starch and sucrose then sift and turbine the grains for a long time so as to make them perfectly spherical.

On tamise à nouveau et on sèche parfaitement.We sift again and dry perfectly.

Dans un mélangeur en acier inoxydable, on projette sur les âmes neutres ainsi obtenues, une solution alcoolique de FENOFIBRATE. In an stainless steel mixer, an alcoholic solution of FENOFIBRATE is sprayed onto the neutral cores thus obtained.

On réalise ensuite la première couche en incorporant à ces microgranules les autres excipients à l'exception de la- gomme laque puis on recommence la pulvérisation de FENOFIBRATE, cet enrobage étant recommencé plusieurs fois avec tamisage et séchage si nécessaire entre chaque couche. The first layer is then produced by incorporating the other excipients with the exception of shellac into these microgranules and then spraying with FENOFIBRATE again, this coating being repeated several times with sieving and drying if necessary between each layer.

Lorsque la première couche contenant le principe actif est terminée on réalise la couche extérieure microporeuse, en projetant sur les granules la gomme laque en solution dans l'alcool éthylique absolu. When the first layer containing the active ingredient is completed, the microporous outer layer is produced, by spraying the granules with shellac in solution in absolute ethyl alcohol.

On sèche ensuite soigneusement en éliminant l'alcool éthylique restant, on tamise à nouveau et on contrôle comme ci-après le titre des microgranules obtenus avant de mettre en gélules, après avoir ajusté eventuellement le titrage par addition et homogénéisé avec des microgranules neutres pour arriver au titrage désiré. It is then carefully dried, eliminating the remaining ethyl alcohol, it is again sieved and the title of the microgranules obtained is checked as below, before putting into capsules, after having optionally adjusted the titration by addition and homogenized with neutral microgranules to arrive at the desired titration.

MESURE DE LA LIBERATION DU FENOFIBRATE
La caractéristique des pores de l'enveloppe extérieure est choisie de façon à assurer une libération retardée de FENOFIBRATE théorique
1ère heure : libération égale à 40 Z
4ème heure : libération égale à 80 Z
8ème heure : libération égale à 100 Z
Pour contrôler cette caractéristique, on utilise un appareil à délitement dans lequel on met en contact une quantité de microgranules correspondant à environ 250 mg de principe actif avec des liquides artificiels, l'appareil permettant de maintenir une agitation constante et une température constante de 370+0,50 C.Les liquides artificiels sont des solutions tam ponnées à pH successifs utilisées selon le schéma ci-dessous
PERIODE SOLUTIONS TEMPS DE LIBERATION pH POURCENTAGE DE
PRINCIPE ACTIF 1 25 ml liquide gastrique 1 heure (le heure) 1,5 40 Z 2 25 ml liquide intestinal 1 heure (2e heure) 4,5 > 40 Z 3 25 ml liquide intestinal 2heures (3 & eheure)6,9 80 Z 4 25 ml liquide intestinal 2heures (5 & eheure)6,9 > 80 % 5 25 ml liquide intestinal 2heures (7 & eheure)7,2 100 Z
MESURE DE BIODISPONIBILITE DE LA NOUVELLE PRESENTATION
Afin de préciser l'intérêt pratique de la nouvelle présentation galénique, il est indispensable de vérifier que la mise à disposition du FENO
FIBRATE par la nouvelle présentation conduit à un taux plasmatique d'acide fénofibrique chez l'homme ayant une signification thérapeutique.MEASURING THE RELEASE OF FENOFIBRATE
The characteristic of the pores of the outer envelope is chosen so as to ensure a delayed release of theoretical FENOFIBRATE
1st hour: release equal to 40 Z
4th hour: release equal to 80 Z
8th hour: release equal to 100 Z
To control this characteristic, a disintegration apparatus is used in which an amount of microgranules corresponding to approximately 250 mg of active principle is brought into contact with artificial liquids, the apparatus making it possible to maintain constant agitation and a constant temperature of 370+ 0.50 C. Artificial liquids are tam solutions calibrated at successive pH used according to the diagram below
PERIOD SOLUTIONS RELEASE TIME pH PERCENTAGE OF
ACTIVE INGREDIENT 1 25 ml gastric fluid 1 hour (hour) 1.5 40 Z 2 25 ml intestinal fluid 1 hour (2nd hour) 4.5> 40 Z 3 25 ml intestinal fluid 2 hours (3 & hour) 6.9 80 Z 4 25 ml intestinal fluid 2 hours (5 & hour) 6.9> 80% 5 25 ml intestinal fluid 2 hours (7 & hour) 7.2 100 Z
BIODAVAILABILITY MEASUREMENT OF THE NEW PRESENTATION
In order to clarify the practical interest of the new galenic presentation, it is essential to verify that the provision of FENO
FIBRATE by the new presentation leads to a plasma level of fenofibric acid in humans having therapeutic significance.

Dans le cadre de la présente invention il était donc nécessaire de vérifier la bioéquivalence de la forme connue et de la nouvelle présentation et d'effectuer une étude pharmacocinétique. In the context of the present invention it was therefore necessary to verify the bioequivalence of the known form and of the new presentation and to carry out a pharmacokinetic study.

La technique de dosage selon Desager (Journal of chromatography (1978) p. 160-64) du métabolite principal l'acide fénofibrique utilise la chromatographie liquide à haute pression : l'étalon interne étant l'acide clofibrique, métabolite principal du clofibrate (DCI). The assay technique according to Desager (Journal of chromatography (1978) p. 160-64) of the main metabolite fenofibric acid uses high-pressure liquid chromatography: the internal standard being clofibric acid, the main metabolite of clofibrate (INN ).

Selon Desager (Int. J. Clin. Pharmacology (1978) p. 570-74) un traitement au long cours par le FENOFIBRATE à raison de 300 à 600 mg par jour en 3 à 6 prises conduit à une concentration à l'équilibre du métabolite actif voisine de 10 microgrammes par litre de plasma. According to Desager (Int. J. Clin. Pharmacology (1978) p. 570-74) long-term treatment with FENOFIBRATE at the rate of 300 to 600 mg per day in 3 to 6 doses leads to an equilibrium concentration of active metabolite close to 10 micrograms per liter of plasma.

Toutefois il est établi que l'activité thérapeutique du FENOFIBRATE est obtenue lorsque la concentration à l'équilibre se situe dans l'intervalle 5 à 15 microgrammes par litre de plasma. However, it is established that the therapeutic activity of FENOFIBRATE is obtained when the concentration at equilibrium is in the range 5 to 15 micrograms per liter of plasma.

Ce résultat à l'équilibre est également obtenu par la forme galénique nouvelle du FENOFIBRATE présenté en microgranules lorsque la concentration est de 200 mg, préférentiellement 250 mg ou même 300 mg de principe actif. This equilibrium result is also obtained by the new dosage form of FENOFIBRATE presented in microgranules when the concentration is 200 mg, preferably 250 mg or even 300 mg of active principle.

La nouvelle forme galénique permet donc d'obtenir un effet identique avec une seule prise quotidienne et une diminution notable de la quantité de principe actif ingérée. The new dosage form therefore makes it possible to obtain an identical effect with a single daily intake and a notable reduction in the amount of active principle ingested.

Par conséquent, on peut affirmer que la nouvelle forme galénique conduit à un nouveau médicament remarquable d'un maniement plus aisé et dont les effets secondaires liés à son utilisation sont diminués. Consequently, it can be said that the new dosage form leads to a remarkable new drug which is easier to use and whose side effects linked to its use are reduced.

Bien entendu, l'homme de l'art pourra trouver d'autres avantages et variantes de l'invention, en particulier en ce qui concerne le procédé d'obtention des microgranules ou les modifications de dosage, sans pour cela sortir du cadre et de la portée de la présente invention.  Of course, those skilled in the art will be able to find other advantages and variants of the invention, in particular with regard to the process for obtaining microgranules or the dosage modifications, without thereby departing from the scope and the scope of the present invention.

Claims (9)

REVENDICATIONS 1. Nouvelle forme galénique du FENOFIBRATE et/ou ses dérivés caractérisée en ce qu'elle est constituée par des microgranules comprenant une âme neutre constituée d'un grain d'un excipient inerte comprenant au moins deux composants du type appartenant à la classe constituée par le saccharose, l'amidon, le talc, la silice desséchante, le lactose et l'acide stéarique, ce grain neutre étant muni d'une première couche comprenant le FENO 1. New dosage form of FENOFIBRATE and / or its derivatives characterized in that it is constituted by microgranules comprising a neutral core consisting of a grain of an inert excipient comprising at least two components of the type belonging to the class constituted by sucrose, starch, talc, drying silica, lactose and stearic acid, this neutral grain having a first layer comprising FENO FIBRATE et/ou ses dérivés, puis d'une seconde couche extérieure constituée par une enveloppe microporeuse comprenant au moins un polymère naturel et/ ou synthétique appartenant à la classe constituée par la gomme laque, la gomme arabique, la gélatine, l'éthylcellulose, l'acétophtalate de cellulose le triacétate de cellulose, le polyjéthylèneglycol, les méthacrylates, le copolymère styrène-acrylonitrite et la polivinylpyrrolidone.FIBRATE and / or its derivatives, then a second outer layer consisting of a microporous envelope comprising at least one natural and / or synthetic polymer belonging to the class consisting of shellac, gum arabic, gelatin, ethylcellulose, cellulose acetophthalate, cellulose triacetate, polyjethylene glycol, methacrylates, styrene-acrylonitrite copolymer and polivinylpyrrolidone. 2. Nouvelle forme galénique du FENOFIBRATE et/ou ses dérivés selon la revendication 1 caractérisée en ce que l'enveloppe microporeuse est formée de gomme laque selon une proportion en poids comprise entre 2 et 10 %. 2. New dosage form of FENOFIBRATE and / or its derivatives according to claim 1 characterized in that the microporous envelope is formed of shellac in a proportion by weight of between 2 and 10%. 3. Nouvelle forme galénique du FENOFIBRATE et/ou ses dérivés selon les revendications 1 et 2 caractérisée en ce que l'excipient inerte de l'âme neutre est un mélange comprenant de 40 à 80 Z en poids de saccharose et de 10 à 40 Z en poids d'amidon. 3. New dosage form of FENOFIBRATE and / or its derivatives according to claims 1 and 2 characterized in that the inert excipient of the neutral core is a mixture comprising from 40 to 80 Z by weight of sucrose and from 10 to 40 Z by weight of starch. 4. Nouvelle forme selon l'une quelconque des revendications 1 à 3 caractérisée en ce que la première couche comprend de 1 à 20 Z en poids de FENOFIBRATEet/ou ses dérivés, de 0,01 Z à 0,5 Z en poids d'acide stéarique, de 5 Z à 15 Z en poids de talc et de 2 à 10 Z en poids de silice desséchante. 4. New form according to any one of claims 1 to 3 characterized in that the first layer comprises from 1 to 20 Z by weight of FENOFIBRATEet / or its derivatives, from 0.01 Z to 0.5 Z by weight of stearic acid, from 5 Z to 15 Z by weight of talc and from 2 to 10 Z by weight of drying silica. 5. Nouvelle forme selon l'une quelconque des revendication 1 å 4 caractérisée en ce que 1'âme neutre comprend des adsorbats de FENOFIBRATE et/ ou ses dérivés. 5. New form according to any one of claims 1 to 4 characterized in that the neutral core comprises adsorbates of FENOFIBRATE and / or its derivatives. 6. Procédé d'obtention de la nouvelle forme galénique selon l'une quelconque des revendications 1 à 5 caractérisé en ce qu'on prépare des microgranules neutres tamisés et séchés, qu'on projette sur ces microgranules une solution dans l'alcool absolu de FENOFIBRATE et/ou ses dérivés, qu'on enrobe ensuite lesdits microgranules par ladite première couche en une ou plusieurs fois puiqu'on forme l'enveloppe microporeuse par enrobage à l'aide dudit polymère en solution dans un solvant. 6. A process for obtaining the new dosage form according to any one of claims 1 to 5 characterized in that neutral sieved and dried microgranules are prepared, which is projected onto these microgranules a solution in absolute alcohol of FENOFIBRATE and / or its derivatives, which said microgranules are then coated with said first layer in one or more times, since the microporous envelope is formed by coating with said polymer in solution in a solvent. 7. Médicaments caractérisés en ce qu'ils comprennent la nouvelle forme galénique d'administration du FENOFIBRATE et/ou ses dérivés sous forme de microgranules conforme à l'une quelconque des revendications 1 à 5 en ce que lesdits microgranules sont mélangés avec des microgranules neutres non enrobés afin d'obtenir une concentration prédéterminée en FENOFIBRATE et/ou ses dérivés. 7. Medicines characterized in that they comprise the new galenical administration form of FENOFIBRATE and / or its derivatives in the form of microgranules according to any one of claims 1 to 5 in that said microgranules are mixed with neutral microgranules uncoated to obtain a predetermined concentration of FENOFIBRATE and / or its derivatives. 8. Médicaments selon la revendication 7 caractérisés en ce qu'ils se présentent sous forme de gélules contenant 200 à 300 mg de FENOFIBRATE. 8. Medicines according to claim 7 characterized in that they are in the form of capsules containing 200 to 300 mg of FENOFIBRATE. 9. Médicaments selon la revendication 7 caractérisés en ce qu'ils se présentent sous forme de comprimés, de suppositoires, de sirop, de granulés, ou de poudre.  9. Medicines according to claim 7 characterized in that they are in the form of tablets, suppositories, syrup, granules, or powder.
FR8024568A 1980-11-19 1980-11-19 Expired FR2494112B1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
FR8024568A FR2494112B1 (en) 1980-11-19 1980-11-19
BE1/10357A BE891129A (en) 1980-11-19 1981-11-16 NEW GALENIC FORM OF FENOFIBRATE, ITS PROCESS FOR OBTAINING ITS APPLICATION AS A MEDICINE
DE19813152519 DE3152519C2 (en) 1980-11-19 1981-11-18 New fenofibrate ready-to-use product with delayed release of active ingredient
AT0906481A AT387517B (en) 1980-11-19 1981-11-18 METHOD FOR PRODUCING A PREPARATION OF PARA-AROYL-PHENOXY-ISOBUTTERIC ACID DERIVATIVES
PCT/FR1981/000148 WO1982001649A1 (en) 1980-11-19 1981-11-18 New galenic preparation of phenofibrate,method for the obtention thereof,its application as a medicine
NL8120434A NL8120434A (en) 1980-11-19 1981-11-18 NEW GALENIC FORM OF PHENOFIBRATE, METHOD OF PREPARATION AND MEDICINAL USE THEREOF.
EP81903096A EP0065531A1 (en) 1980-11-19 1981-11-18 New galenic preparation of phenofibrate, method for the obtention thereof, its application as a medicine
IT25185/81A IT1144948B (en) 1980-11-19 1981-11-19 NEW GALENIC FORM OF PHENOFIBRATE, ITS PROCESS TO OBTAIN IT, ITS APPLICATION AS A MEDICINAL PRODUCT

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US7976869B2 (en) 2001-01-22 2011-07-12 Laboratoires Fournier S.A. Fenofibrate tablets
WO2004028506A1 (en) * 2002-09-24 2004-04-08 Ranbaxy Laboratories Limited Oral pharmaceutical compositions of fenofibrate having high bioavailability
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AT387517B (en) 1989-02-10
IT1144948B (en) 1986-10-29
WO1982001649A1 (en) 1982-05-27
ATA906481A (en) 1988-07-15
DE3152519T1 (en) 1983-12-29
BE891129A (en) 1982-05-17
EP0065531A1 (en) 1982-12-01
DE3152519C2 (en) 1990-11-22
FR2494112B1 (en) 1986-01-10
IT8125185A0 (en) 1981-11-19
NL8120434A (en) 1982-10-01

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