CA1293194C - Medicine based on fenofibrate, and a method of preparing it - Google Patents
Medicine based on fenofibrate, and a method of preparing itInfo
- Publication number
- CA1293194C CA1293194C CA000543882A CA543882A CA1293194C CA 1293194 C CA1293194 C CA 1293194C CA 000543882 A CA000543882 A CA 000543882A CA 543882 A CA543882 A CA 543882A CA 1293194 C CA1293194 C CA 1293194C
- Authority
- CA
- Canada
- Prior art keywords
- fenofibrate
- medicine
- inert
- sugar
- binder
- 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.)
- Expired - Lifetime
Links
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Hematology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A B S T R A C T
A granular medicine based on fenofibrate, each granule comprising an inert core, a layer based on fenofibrate, and a protective layer, the medicine being characterized in that the fenofibrate in the layer based on fenofibrate is present in the form of crystalline microparticles of dimensions not greater than 30 microns, and preferably less than 10 microns.
A granular medicine based on fenofibrate, each granule comprising an inert core, a layer based on fenofibrate, and a protective layer, the medicine being characterized in that the fenofibrate in the layer based on fenofibrate is present in the form of crystalline microparticles of dimensions not greater than 30 microns, and preferably less than 10 microns.
Description
~2~
A MEDICINE BASED ON FENOFIB~ATE, AND A METHOD OF PREPARING IT
The present invention relates to a medicine based on fenofibrate, and also to a method of preparing it.
BACKGROUND OF THE INVENTION
It is recalled that fenofibrate is isopropyl para-(4-chlorobenzoyl)-pehnoxyisobutyrate. In the present application, the term "fenofibrate and its derivatives" is usad -to designa-te compounds having formula I:
~ CH3 10 (I) R1 - CO ~ O - C CO - Y
R3 (~H3 in which:
R1 represents a phenyl group or a phenyl group substituted by one or more -CH3, CF3 or by halogens (in 15 particular fluorine, chlorine, or bromine);
R2 and R3 independently represent a hydrogen atom or a halogen atom (preferably fluorine, chlorine, or bromine), an alkyl or an alkoxy group having 1 to 5 C or one of the following groups: -CF3, -SCH3, -SOCH3, -S02CH3, or -OH; and Y represents one of the following groups: -OH; inferior alkoxy, preferably in Cl - C4; -NR~Rs; -NHCH2C~l2NR4Rs; or -O-alkylene-NR4Rs, with the alkylene having, in particular, two-to six atoms of carbon, and with R4 and Rs being identical or different and each representing a hydrogen atom or one of the 25 following groups: Cl - Cs alkyl, C3 - C7 and preferably Cs - C6 cycloalkyl; aryl or aryl substituted on the aromatic residue by one or more halogen~ methylr or CF3 groups; or else R4 and Rs constitute, together with the nitrogen atom to which they are connected, one of the following groups: either an n-hetero~
30 cyclic group having 5 to 7 vertices capable of enclosing a second hetero-atom selected from N, O, and S, and capable of being substituted; or else an amide residue derived from lysine or cysteine.
Naturally, the expression "fenofibrate and its derivatives"
also covers the salts that can be obtairled from compounds of formula 1 by adding pharmaceutically acceptable acids.
3~
Fenofibrate is used in the treatment of adult endegenous hyperlipidasmia, hypercholesterolaemia, and hypertrigylcerid-aemia. Thus, in an adult be:ing treated with 300 to 400 mg per day of fenofibrate, there can be observed a 20% to 25~
5 reduction in cholesterolaemia and a 40% to 50% reduction in triglyceridaemia.
The unaltered substance is not found in plasma. The ma~or plasmatic metabolite is fenofibric acid.
On average, the maximum concentration in plasma i~ reached 10 five hours after taking the medicine. The average concentration in plasma is about 50 micrograms/ml for a dose of 300 mg o~
fenofibrate per day. This level is stable throughout continuous treatment.
Fenofibric acid is strongly bound -to plasmatic albumin and 15 can displace antivitamins K from protein fi~ing sites and potentialize their anticoagulant effect.
The half-life for eliminating fenofibric acid from plasma is about twenty hours.
Under these conditions, it will be understood that there 20 is no need to take it more than once a day.
It has been observed that fenofibrate has poor solubility in aqueous liquids, theraby giving rise to non~uniform absorption in the digestive tube, and in accordance with the present invention a galenical preparation has been devised 25 which considerably improves absorption by the digestive tube.
SUMMARY OF THE INVENTION
The present invention provides a medicine based on fenofibrate and in the form of granules, each granule comprising an inert core, a layer based on fenofibrate, and a 30 protective layer. In the layer based on fenofibrate, the fenofibrate is present in -the form of crystalline microparticles of dimensions not greater than 30 microns, and preferably less than 10 microns.
In accordance with the present invention, this structure 35 is obtained by a method includiny a step of pro;ecting a damp and s-ticky outer layer onto the inert cores, followed by a step of projecting fenofibrate microparticles onto the damp layer with the dampness being rapidly evaporated in order to prevent it from dissolvlng the fenofibrate microparticles while never-tha-less ~ixing said feno~ibrate microparticles onto the cores, with said two steps being repeated until a su~ficient quantity 5 of fenofibrate has been fixed onto the cores.
The damp and s-ticky layer may advantageously be constituted by a solution of a polymer in alcohol or by an aqueous suspen-sion o~ the polymer, and the alcohol solution may be prepared using alcohols which are commonly used ln pharmacology.
MORE DETAILED DESCRIPTION
There follows a description, by way of example, of the manufacture of one embodiment of a medicine in accordance with the present invention.
Inert grains for forming the inert cores are prepared in 15 conventional manner. For example, each grain may be a sucrose crystal having a diameter of 0.3 mm. A suspension of maize starch is sprayed onto the crystals, the suspension comprising 27~ by weight of maize starch in a hot sugar solution (prepared, for example, by dissolving 73 kg of sugar in 32 kg 20 of water: 27 kg starch, 73 kg sugar, 32 kg water). The sugar solution is pro~ected at 50C into a turbine which is itself heated to 50C. The ~uantity projected is adjusted so that the diameter o~ each grain increases from 0.3 mm to 0.6 mm, with the grain having about 25~ by weight starch and about 75%
25 sucrose, once the water has evaporated ~rom the sugar solution.
Thereafter, the inert cores are rotated in a turbine and they are dampened with an alcohol solution containing 12.5% by weight of a methacrylic polymer ~95 alcohol). The grains become damp and stick~. Fenofibrate powder is then pro~ected 30 onto them, with the powder being obtained by crushing feno~ibrate crystals until microparticles are obtained. A
typical powder haR the following partical size distribution:
100% < 30 microns 99.5% < 20 microns 98~ < 10 microns 88% < 5 microns.
The grains are then immediately dried very rapidly in order to :~?J~ lL9~
prevent the alcohol from having enough time to dissolve the feno~brate (a flow of air is passed through the turbine).
This avoids destroying the microparticulate structure which offers a considerable area for encouraging absorption. A
5 singl0 thickness of microparticles ls thus deposited on the sticky grain where the micropartiales are fixed b~ adherence.
The operations of dampening-pro~ecting-drying may be performed in about one or two minutes. These operations of dampening the core and projecting micropartlcles are repea-ted until all of 10 the powder has b~en incorporated.
Finally, a protec-tive coatlng is applied, e.g. a thin layer of methacrylic pol~ner, representing about 1% by weight of each granule.
~ ranules obtained in this way are pu-t into capsules, with 15 a dose of 250 mg of fenofibra-ts per capsule.
The fenofibrate layer structure is similar to that of a sponge, with the pores containing microparticles of fenofibrate.
The sponge is constituted by a binder which is soluble in an aqueous medium: methacrylate or polyvinylpyrolidone. Once the 20 binder has dissolved, the microparticles of fenofibrate are released and can present their entire areas to the process of absorption in the intestinal aqueous medium.
One example of fonnulation is as follows:
- fenofibrate : 400 kg inert grains : 110 kg (sugar and/or starch) polyvinylpyrolidone and/or methaoryla-te : 20 kg Of the last 20 kg, about 5 kg are used for making the protective envelope (about 1~ of the total weigh-t) and the 30 remainder (about 15 kg) is used for binding the microparticles of fenofibrate, with alcohol belng used temporarily as the solvent.
The quantity of binder is determined so that at least 55 of the fenofibrate is released in one hour in a water based 35 liquid medium.
This fraction can be measured as follows: the contents of a capsule is placed in a flask containing 35 ml of a medium .; .
311~
having a pH of 1~5. The flask is stirred at 30 rpm and at 37C. After stirring for one hour, the percentage of feno-fibrate -that has been released from the galenical preparation in accordance with the invention is greater than 65~.
Composition of the mediurn:
118 ml normal hydrochloric acid 84 ml solution of normal sodium hydroxide distilled water: enough -to obtain 1000.0 ml of medium.
The pH of the medium lies between 1.45 and 1.55.
Medicines in accordance with the invention have also shown reductions in variability of blood concentrations both inter and intra patien-t (i.e. on the same patient or between different patients).
A MEDICINE BASED ON FENOFIB~ATE, AND A METHOD OF PREPARING IT
The present invention relates to a medicine based on fenofibrate, and also to a method of preparing it.
BACKGROUND OF THE INVENTION
It is recalled that fenofibrate is isopropyl para-(4-chlorobenzoyl)-pehnoxyisobutyrate. In the present application, the term "fenofibrate and its derivatives" is usad -to designa-te compounds having formula I:
~ CH3 10 (I) R1 - CO ~ O - C CO - Y
R3 (~H3 in which:
R1 represents a phenyl group or a phenyl group substituted by one or more -CH3, CF3 or by halogens (in 15 particular fluorine, chlorine, or bromine);
R2 and R3 independently represent a hydrogen atom or a halogen atom (preferably fluorine, chlorine, or bromine), an alkyl or an alkoxy group having 1 to 5 C or one of the following groups: -CF3, -SCH3, -SOCH3, -S02CH3, or -OH; and Y represents one of the following groups: -OH; inferior alkoxy, preferably in Cl - C4; -NR~Rs; -NHCH2C~l2NR4Rs; or -O-alkylene-NR4Rs, with the alkylene having, in particular, two-to six atoms of carbon, and with R4 and Rs being identical or different and each representing a hydrogen atom or one of the 25 following groups: Cl - Cs alkyl, C3 - C7 and preferably Cs - C6 cycloalkyl; aryl or aryl substituted on the aromatic residue by one or more halogen~ methylr or CF3 groups; or else R4 and Rs constitute, together with the nitrogen atom to which they are connected, one of the following groups: either an n-hetero~
30 cyclic group having 5 to 7 vertices capable of enclosing a second hetero-atom selected from N, O, and S, and capable of being substituted; or else an amide residue derived from lysine or cysteine.
Naturally, the expression "fenofibrate and its derivatives"
also covers the salts that can be obtairled from compounds of formula 1 by adding pharmaceutically acceptable acids.
3~
Fenofibrate is used in the treatment of adult endegenous hyperlipidasmia, hypercholesterolaemia, and hypertrigylcerid-aemia. Thus, in an adult be:ing treated with 300 to 400 mg per day of fenofibrate, there can be observed a 20% to 25~
5 reduction in cholesterolaemia and a 40% to 50% reduction in triglyceridaemia.
The unaltered substance is not found in plasma. The ma~or plasmatic metabolite is fenofibric acid.
On average, the maximum concentration in plasma i~ reached 10 five hours after taking the medicine. The average concentration in plasma is about 50 micrograms/ml for a dose of 300 mg o~
fenofibrate per day. This level is stable throughout continuous treatment.
Fenofibric acid is strongly bound -to plasmatic albumin and 15 can displace antivitamins K from protein fi~ing sites and potentialize their anticoagulant effect.
The half-life for eliminating fenofibric acid from plasma is about twenty hours.
Under these conditions, it will be understood that there 20 is no need to take it more than once a day.
It has been observed that fenofibrate has poor solubility in aqueous liquids, theraby giving rise to non~uniform absorption in the digestive tube, and in accordance with the present invention a galenical preparation has been devised 25 which considerably improves absorption by the digestive tube.
SUMMARY OF THE INVENTION
The present invention provides a medicine based on fenofibrate and in the form of granules, each granule comprising an inert core, a layer based on fenofibrate, and a 30 protective layer. In the layer based on fenofibrate, the fenofibrate is present in -the form of crystalline microparticles of dimensions not greater than 30 microns, and preferably less than 10 microns.
In accordance with the present invention, this structure 35 is obtained by a method includiny a step of pro;ecting a damp and s-ticky outer layer onto the inert cores, followed by a step of projecting fenofibrate microparticles onto the damp layer with the dampness being rapidly evaporated in order to prevent it from dissolvlng the fenofibrate microparticles while never-tha-less ~ixing said feno~ibrate microparticles onto the cores, with said two steps being repeated until a su~ficient quantity 5 of fenofibrate has been fixed onto the cores.
The damp and s-ticky layer may advantageously be constituted by a solution of a polymer in alcohol or by an aqueous suspen-sion o~ the polymer, and the alcohol solution may be prepared using alcohols which are commonly used ln pharmacology.
MORE DETAILED DESCRIPTION
There follows a description, by way of example, of the manufacture of one embodiment of a medicine in accordance with the present invention.
Inert grains for forming the inert cores are prepared in 15 conventional manner. For example, each grain may be a sucrose crystal having a diameter of 0.3 mm. A suspension of maize starch is sprayed onto the crystals, the suspension comprising 27~ by weight of maize starch in a hot sugar solution (prepared, for example, by dissolving 73 kg of sugar in 32 kg 20 of water: 27 kg starch, 73 kg sugar, 32 kg water). The sugar solution is pro~ected at 50C into a turbine which is itself heated to 50C. The ~uantity projected is adjusted so that the diameter o~ each grain increases from 0.3 mm to 0.6 mm, with the grain having about 25~ by weight starch and about 75%
25 sucrose, once the water has evaporated ~rom the sugar solution.
Thereafter, the inert cores are rotated in a turbine and they are dampened with an alcohol solution containing 12.5% by weight of a methacrylic polymer ~95 alcohol). The grains become damp and stick~. Fenofibrate powder is then pro~ected 30 onto them, with the powder being obtained by crushing feno~ibrate crystals until microparticles are obtained. A
typical powder haR the following partical size distribution:
100% < 30 microns 99.5% < 20 microns 98~ < 10 microns 88% < 5 microns.
The grains are then immediately dried very rapidly in order to :~?J~ lL9~
prevent the alcohol from having enough time to dissolve the feno~brate (a flow of air is passed through the turbine).
This avoids destroying the microparticulate structure which offers a considerable area for encouraging absorption. A
5 singl0 thickness of microparticles ls thus deposited on the sticky grain where the micropartiales are fixed b~ adherence.
The operations of dampening-pro~ecting-drying may be performed in about one or two minutes. These operations of dampening the core and projecting micropartlcles are repea-ted until all of 10 the powder has b~en incorporated.
Finally, a protec-tive coatlng is applied, e.g. a thin layer of methacrylic pol~ner, representing about 1% by weight of each granule.
~ ranules obtained in this way are pu-t into capsules, with 15 a dose of 250 mg of fenofibra-ts per capsule.
The fenofibrate layer structure is similar to that of a sponge, with the pores containing microparticles of fenofibrate.
The sponge is constituted by a binder which is soluble in an aqueous medium: methacrylate or polyvinylpyrolidone. Once the 20 binder has dissolved, the microparticles of fenofibrate are released and can present their entire areas to the process of absorption in the intestinal aqueous medium.
One example of fonnulation is as follows:
- fenofibrate : 400 kg inert grains : 110 kg (sugar and/or starch) polyvinylpyrolidone and/or methaoryla-te : 20 kg Of the last 20 kg, about 5 kg are used for making the protective envelope (about 1~ of the total weigh-t) and the 30 remainder (about 15 kg) is used for binding the microparticles of fenofibrate, with alcohol belng used temporarily as the solvent.
The quantity of binder is determined so that at least 55 of the fenofibrate is released in one hour in a water based 35 liquid medium.
This fraction can be measured as follows: the contents of a capsule is placed in a flask containing 35 ml of a medium .; .
311~
having a pH of 1~5. The flask is stirred at 30 rpm and at 37C. After stirring for one hour, the percentage of feno-fibrate -that has been released from the galenical preparation in accordance with the invention is greater than 65~.
Composition of the mediurn:
118 ml normal hydrochloric acid 84 ml solution of normal sodium hydroxide distilled water: enough -to obtain 1000.0 ml of medium.
The pH of the medium lies between 1.45 and 1.55.
Medicines in accordance with the invention have also shown reductions in variability of blood concentrations both inter and intra patien-t (i.e. on the same patient or between different patients).
Claims (18)
1.- Medicine in the form of granules with controlled release of fenofibrate, each granule comprising an inert core, a layer based on fenofibrate and a protective layer, wherein the improvement comprises the layer based on fenofibrate containing the fenofibrate in the form of crystalline microparticles of dimensions not greater than 30 microns, said microparticles being included in the pores of an inert matrix soluble in water.
2.- A medicine according to claim 1, wherein inert inert matrix is composed by a binder selected from the group comprising: methacrylic polymers, polyvinylpyrolidone, mixtures thereof; cellulose derivatives; and polyethylene glycols.
3.- A medicine according to claim 1, wherein the inert core has a diameler of about 0.3 mm to about 0.6 mm and is constituted by a substance selected from thegroup comprising: glucose, sucrose, lactose, and their equivalents, and starch, and mixtures thereof.
4.- A medicine according to claim 1, wherein the protective layer represents about 1% by weight of each granule, and is formed of a substance selected from the group comprising: methacrylic polymers, polyvinylpyrolidone, mixtures thereof;
cellulose derivatives; and polyethylene glycols.
cellulose derivatives; and polyethylene glycols.
5.- A medicine according to claim 1, wherein the quantity of binder is such that the quantity of fenofibrate liberated in one hour in an aqueous liquid is not less than 65%.
6.- A medicine according to claim 1, wherein the dimensions of said microparticles are less than 10 microns.
7.- A medicine according to claim 3, wherein the starch is maize starch.
8.- A method for preparing a medicine involving a controlled release of fenofibrate in aqueous medium, said medicine being in the form of a granule thatcomprises an inert core in its center, a protective outer coating and an intermediate layer based on fenofibrate, said process comprising forming said intermediate layer on said inert core by a process comprising performing in a time duration of the order of one or two minutes three sequential steps (i), (ii) and (iii) as follows:
(i) dampening said inert core with a solution based on a binder soluble in water and comprising a solvent selected from the group consisting of water and alcohols, (ii) then projecting onto said dampened core in a single layer fenofibrate cryslalline microparticles that have diameters less than 30 microns, (iii) and thereafter drying before said solution based on said binder dissolves said fenofibratc micropat1icles, and repeating said three steps in sequence until said intermediate layer is formed so that said fenofibrate microparticles therein are included in the pores of an inert matrix constituted by said binder.
(i) dampening said inert core with a solution based on a binder soluble in water and comprising a solvent selected from the group consisting of water and alcohols, (ii) then projecting onto said dampened core in a single layer fenofibrate cryslalline microparticles that have diameters less than 30 microns, (iii) and thereafter drying before said solution based on said binder dissolves said fenofibratc micropat1icles, and repeating said three steps in sequence until said intermediate layer is formed so that said fenofibrate microparticles therein are included in the pores of an inert matrix constituted by said binder.
9.- A method according to claim 8, wherein said binder constituting said inert matrix is a substance selected from the group consisting of rnethacrylic polymers, polyvinylpyrolidone, mixtures of methacrylic polymers and polyvinylpyrolidone, and cellulose derivatives and polyethylene glycols.
10.- A method according to claim 8, wherein said inert core is prepared by spraying an aqueous sugar solution containing a starch suspension at about 50°C
onto sugar crystals having a diameter of about 0.3 mm until their diameter reaches about 0.6 mm.
onto sugar crystals having a diameter of about 0.3 mm until their diameter reaches about 0.6 mm.
11.- A method according to claim 10, wherein said sugar in said crystals having a diameter of about 0.3 mm is selected from the sugar group consisting ofglucose, sucrose, lactose, and their equivalents.
12.- A method according to claim 10, wherein said starch in said suspension is maize starch.
13.- A method according to claim 10, wherein said inert core comprises about 25% by weight starch and about 75 % by weight sugar.
14.- A method according to claim 8, wherein said protective outer layer is made of a substance selected from the group consisting of methacrylic polymers, polyvinylpyrolidone, mixtures of methacrylic polymers and polyvinylpyrolidone, and cellulose derivatives and polyethylene glycols.
15.- A method according to claim 8, wherein said protective outer layer represents about 1% by weight of said granule.
16.- A method according to claim 8, wherein said process is conducted in a turbine, and said drying operation is carried out with the help of an air flow.
17.- A method according to claim 8, wherein said process is repeated until said intermediate layer contains a quantity of said binder such that the quantity of fenofibrate released in one hour in an aqueous medium is greater than 65%.
18.- A method according to claims 10, wherein said sugar in said aqueous solution is selected from the sugar group consisting of glucose, sucrose, lactose, and their equivalents.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8611540A FR2602423B1 (en) | 1986-08-08 | 1986-08-08 | PROCESS FOR THE PREPARATION OF A FENOFIBRATE-BASED MEDICINAL PRODUCT, OBTAINED BY THIS PROCESS |
| FR8611540 | 1986-08-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1293194C true CA1293194C (en) | 1991-12-17 |
Family
ID=9338169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000543882A Expired - Lifetime CA1293194C (en) | 1986-08-08 | 1987-08-06 | Medicine based on fenofibrate, and a method of preparing it |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US4800079A (en) |
| EP (1) | EP0256933B1 (en) |
| JP (1) | JP2571693B2 (en) |
| AT (1) | ATE75940T1 (en) |
| AU (1) | AU601462B2 (en) |
| CA (1) | CA1293194C (en) |
| DE (1) | DE3779009D1 (en) |
| DK (1) | DK175867B1 (en) |
| ES (1) | ES2041699T3 (en) |
| FR (1) | FR2602423B1 (en) |
| GR (1) | GR3004698T3 (en) |
| NO (1) | NO174876C (en) |
| ZA (1) | ZA875758B (en) |
Families Citing this family (107)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2602423B1 (en) * | 1986-08-08 | 1989-05-05 | Ethypharm Sa | PROCESS FOR THE PREPARATION OF A FENOFIBRATE-BASED MEDICINAL PRODUCT, OBTAINED BY THIS PROCESS |
| FR2627696B1 (en) * | 1988-02-26 | 1991-09-13 | Fournier Innovation Synergie | NEW GALENIC FORM OF FENOFIBRATE |
| ATE156707T1 (en) * | 1991-06-21 | 1997-08-15 | Ilsan Ilac Ve Hammaddeleri San | NEW GALENIC PROCESS FOR PELLETS CONTAINING OMEPRAZOLE |
| US5167964A (en) * | 1992-02-14 | 1992-12-01 | Warner-Lambert Company | Semi-enteric drug delivery systems and methods for preparing same |
| US5571531A (en) * | 1994-05-18 | 1996-11-05 | Mcmaster University | Microparticle delivery system with a functionalized silicone bonded to the matrix |
| FR2730231B1 (en) * | 1995-02-02 | 1997-04-04 | Fournier Sca Lab | COMBINATION OF FENOFIBRATE AND VITAMIN E, USE IN THERAPEUTICS |
| DK0824344T3 (en) * | 1995-05-09 | 2005-08-15 | Phoqus Pharmaceuticals Ltd | Powdered composition for electrostatic coating of pharmaceutical substrates |
| US7008668B2 (en) * | 1995-05-09 | 2006-03-07 | Phoqus Pharmaceuticals Limited | Powder coating composition for electrostatic coating of pharmaceutical substrates |
| FR2737121B1 (en) * | 1995-07-27 | 1997-10-03 | Cl Pharma | NEW GALENIC FORMULATIONS OF FENOFIBRATE AND THEIR APPLICATIONS |
| DE19608750A1 (en) * | 1996-03-06 | 1997-09-11 | Durachemie Gmbh & Co Kg | Process for the production of fenofibrate preparations |
| US6465016B2 (en) | 1996-08-22 | 2002-10-15 | Research Triangle Pharmaceuticals | Cyclosporiine particles |
| US7255877B2 (en) * | 1996-08-22 | 2007-08-14 | Jagotec Ag | Fenofibrate microparticles |
| ZA978537B (en) | 1996-09-23 | 1998-05-12 | Focal Inc | Polymerizable biodegradable polymers including carbonate or dioxanone linkages. |
| GB9623634D0 (en) * | 1996-11-13 | 1997-01-08 | Bpsi Holdings Inc | Method and apparatus for the coating of substrates for pharmaceutical use |
| FR2758459B1 (en) | 1997-01-17 | 1999-05-07 | Pharma Pass | FENOFIBRATE PHARMACEUTICAL COMPOSITION HAVING HIGH BIODAVAILABILITY AND PROCESS FOR PREPARING THE SAME |
| US6979456B1 (en) | 1998-04-01 | 2005-12-27 | Jagotec Ag | Anticancer compositions |
| DE69914742T2 (en) | 1998-05-29 | 2004-11-25 | Skyepharma Canada Inc., Verdun | MICROPARTICLES PROTECTED AGAINST HEAT AND METHOD FOR TERMINAL STEAM STERILIZATION THEREOF |
| WO2000010531A1 (en) | 1998-08-19 | 2000-03-02 | Rtp Pharma Inc. | Injectable aqueous dispersions of propofol |
| ID29270A (en) * | 1998-11-20 | 2001-08-16 | Rtp Pharma Inc | MICRO PARTICLES THAT ARE STABILIZED BY PHOSPHOLIPIDS THAT CAN SPREAD |
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-
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-
1987
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- 1987-08-05 AU AU76603/87A patent/AU601462B2/en not_active Expired
- 1987-08-06 ES ES198787401824T patent/ES2041699T3/en not_active Expired - Lifetime
- 1987-08-06 EP EP87401824A patent/EP0256933B1/en not_active Expired - Lifetime
- 1987-08-06 DE DE8787401824T patent/DE3779009D1/en not_active Expired - Lifetime
- 1987-08-06 AT AT87401824T patent/ATE75940T1/en not_active IP Right Cessation
- 1987-08-06 CA CA000543882A patent/CA1293194C/en not_active Expired - Lifetime
- 1987-08-07 NO NO873320A patent/NO174876C/en not_active IP Right Cessation
- 1987-08-07 JP JP62196510A patent/JP2571693B2/en not_active Expired - Lifetime
- 1987-08-07 DK DK198704118A patent/DK175867B1/en not_active IP Right Cessation
- 1987-08-10 US US07/083,409 patent/US4800079A/en not_active Expired - Lifetime
-
1988
- 1988-10-12 US US07/256,836 patent/US4961890A/en not_active Expired - Lifetime
-
1992
- 1992-05-26 GR GR920401032T patent/GR3004698T3/el unknown
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|---|---|
| ES2041699T3 (en) | 1993-12-01 |
| EP0256933A1 (en) | 1988-02-24 |
| US4800079A (en) | 1989-01-24 |
| US4961890A (en) | 1990-10-09 |
| NO873320L (en) | 1988-02-09 |
| AU7660387A (en) | 1988-02-11 |
| AU601462B2 (en) | 1990-09-13 |
| EP0256933B1 (en) | 1992-05-13 |
| NO174876B (en) | 1994-04-18 |
| NO873320D0 (en) | 1987-08-07 |
| ATE75940T1 (en) | 1992-05-15 |
| JPS6348212A (en) | 1988-02-29 |
| FR2602423A1 (en) | 1988-02-12 |
| NO174876C (en) | 1994-07-27 |
| DK175867B1 (en) | 2005-04-18 |
| DE3779009D1 (en) | 1992-06-17 |
| GR3004698T3 (en) | 1993-04-28 |
| DK411887A (en) | 1988-02-09 |
| FR2602423B1 (en) | 1989-05-05 |
| DK411887D0 (en) | 1987-08-07 |
| ZA875758B (en) | 1988-04-27 |
| JP2571693B2 (en) | 1997-01-16 |
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