SK3552001A3 - Method for preparing novel fenofibrate galenic formulations, galenic formulations obtained and applications - Google Patents

Abstract

The invention concerns a method for preparing novel galenic formulations for providing fenofibrate with enhanced bioavailability when it is orally absorbed, and consisting in: (a) micronizing fenofibrate; (b) granulating the fenofibrate in the presence of a liquid medium comprising a surfactant, water and water-miscible alcohol; and (c) drying the resulting granular material. The invention also concerns the galenic formulations obtained by said method. Said formulations are used for preparing a medicine for oral administration and comprising fenofibrate as active principle, in particular for treating hypercholesterolemia and hypertriglyceridemia.

Description

Technical field

The present invention relates to a process for the preparation of galenic forms containing fenofibrate as an active ingredient which, when administered orally, achieve a significantly higher bioavailability compared to the currently available pharmaceutical formulations containing fenofibrate. The invention also relates to galenic forms prepared by said method, as well as to the application of said method and described galenic forms, in particular in the preparation of medicaments for oral administration.

BACKGROUND OF THE INVENTION

Fenofibrate (INN) or isopropyl 2- (4- (4-chlorobenzoyl) phenoxy) -2-methylpropionate is one of the most commonly used hypolipidemics in the treatment of isolated or combined endogenous hypercholesterolemia and adult hypertryglyceridemia. Its efficacy has been conclusively confirmed in these therapeutic indications. Fenofibrate reduces cholesterolemia by 20 - 25% and triglyceridemia by 40 - 50% when administered at therapeutic doses for a long time, the effect of treatment is evident from the first month of treatment.

Fenofibrate was first marketed in France in 1975 in the form of gelatin capsules containing 100 mg of the active substance (LIPANTHYL® 100). The preparation was administered at a dose of 3 to 4 gelatin capsules per day between meals, which corresponded to a daily dose of 300 to 400 mg of the active ingredient. This patented product is still distributed in France but under the name SECALIP® 100.

In 1986, a form intended for patients requiring a dose of only 300 mg fenofibrate per day was introduced. It was distributed as gelatin capsules containing 300 mg of the active substance (LIPANTHYL® 300). Dosage - in this case, one capsule a day should improve patient compliance. This dosage was possible due to the long-lasting effect of fenofibrate, whose half-life is approximately 20 hours.

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In France, this patented medical product is still available under the renamed SECALIP® 300.

The scientific work of DESAGER et al. (J. Clin. Pharmacol. 1978, 26, 570-574) and WEIL et al. (Drug metabolism, 1980, 18, 115-120) have shown that the intestinal absorption of fenofibrate in solid form (powder or granules) is very poor. Fenofibric acid, the major active metabolite, is only present in plasma when administered fenofibrate on an empty stomach in an amount corresponding to approximately 20% of the original dose of fenofibrate and 60%, respectively, when administered with food. The second figure was subsequently confirmed by the work of STROLIN BENEDETTI et al. (Acta Pharmacol. Toxicol., 1986, 59, suppl. 5, 167), which showed that after taking a gelatin capsule containing 300 mg fenofibrate with food, it effectively absorbs and only about 60% of the administered dose gets fenofibric acid into the bloodstream. fenofibrate.

In addition, long-term use of fenofibrate has been found not to be completely devoid of adverse effects. Cases of muscle affections (diffuse myalgia, hyperalgia / hypersensitivity, rhabdomyolysis, etc.), digestive problems, rise in transaminases (hepatic enzymes), biliary lithiasis have been reported to require discontinuation of treatment.

Therefore, several scientific studies have been conducted to create galenic forms that increase the oral bioavailability of fenofibrate, thereby reducing the dose of fenofibrate required to achieve a therapeutic effect and consequently reduce the risk of adverse reactions.

French patent application no. 80 24568, filed in 1980 by Claude LARUELLE and DESHORS, represents the first technological advancement in this regard. The patent discloses a galenic form in the form of granules consisting of a neutral core coated with a middle layer containing fenofibrate and an outer, protective layer composed of a polymer suitable for oral administration. The granules described make it possible to obtain therapeutically effective levels of fenofibric acid when administered once a day after filling into gelatin capsules at a dose of 250 mg.

European patent application no. No. 256,933, filed in 1987 by Applicant ETHYPHARM, is a galenic form promoting, in particular, intestinal absorption of fenofibrate. Also, this form contains granules composed of a neutral core, a medium fenofiber and an outer protective layer, but with the hundredth difference that

-3 ······························· In these granules, fenofibrate is present in the form of crystalline particles up to 50 µm, preferably 10 µm.

French patent application no. 88 02359, filed in 1988 by Applicant FOURNIER INNOVATION ET SYNERGIE, represents, in part, a therapeutic composition in the form of gelatin capsules dosed with 200 mg of fenofibrate containing comicronized fenofibrate and a solid surfactant. Undoubtedly, this therapeutic mixture, launched on the French market in 1991 under the name LIPANTHYL® 200 Micronisé, represents a significant advance. Scientific studies have shown that, in terms of biological kinetics, such a gelatin capsule (LIPANTHYL® 200 Micronisé) corresponds to a gelatin capsule LIPANTHYL® 300 (GUICHARD and LEVY-PRADES SAURON, J. Int. Med., 1991, 48-50) as well as a gelatin capsule. LIPANTHYL® 200 Micronisé equivalent of 3 gelatin capsules LIPANTHYL® 100 (Laboratoires FOURNIER, LIPANTHYL, Documentation Scientiflque and Technique aux aux Pharmaciens des Hôpitaux et Desablissements de soins (Scientific and Technical Documentation for Physicians in Hospitals, Healthcare, 1992)

In addition, BRODIE et al. (Arzneimittel Forschung, 1976, 26, 896-901) have shown that administration of fenofibrate, the molecule of which is lipophilic, in sunflower oil allows almost complete intestinal absorption of the active ingredient, as opposed to the administration of fenofibrate in solid form. However, it has been found that sunflower oil is not suitable as a solvent for the manufacture of medicaments. Dissolving the required dose of fenofibrate would require a relatively large volume of oil, of the order of 5 ml, which does not allow the manufacture of capsules with dimensions acceptable to patients.

International patent application WO 96/21439, filed in 1996 by GALEPHAR P.R., proposed the preparation of a medicament in the form of gelatin capsules filled with a mixture containing fenofibrate dissolved in polyglycosylated glycerides such as e.g. mixtures of glycerol and fatty acid esters or polyethylene glycol and fatty acid esters. As disclosed in this patent application, 3 gelatin capsules of such a preparation dosed at 67 mg of fenofibrate would be biologically equivalent to 3 LIPANTHYL® 100 gelatin capsules and at the same time one gelatin capsule with a 200 mg dose of fenofibrate of such preparation would be biologically equivalent to one LIPANTH® gelatin capsule. 200 Micronisé.

In parallel, in French patent application no. 95 09142 filed in 1995

-4 ·· ·· ··················· I * I · I · I · · · ···· CL PHARMA has been proposed to improve the solubility of fenofibrate and hence its bioavailability by administration in the form of soft capsules in which fenofibrate would be dissolved in a nonionic and amphiphilic surfactant, in particular diethylene glycol monoethyl ether. This galenic form makes it possible to achieve therapeutically effective plasma concentrations of fenofibric acid when administered daily with 100 mg of fenofibrate. However, the cost of producing such capsules greatly limits the benefits of their potential use.

SUMMARY OF THE INVENTION

However, in the context of their research on increasing the bioavailability of fenofibrate, the authors observed a surprising fact. They have found that it is possible to obtain solid-state galenic forms which provide a much higher oral bioavailability of fenofibrate than presently available fenofibrate pharmaceutical compositions. That is, they make it possible to obtain the same therapeutic benefit by using substantially lower doses of the active ingredient by subjecting the micronized fenofibrate to a granulation process in the presence of a liquid medium containing water, a water miscible alcohol and a surfactant, and subsequently drying the material.

It is therefore an object of the present invention to provide a process for the preparation of a galenic form comprising fenofibrate as an active ingredient, which process is characterized in that:

(a) micronizing fenofibrate, (b) micronized fenofibrate granules in the presence of a liquid medium containing surfactant, water and water miscible with alcohol, and (c) drying the granular material so obtained.

The present invention further comprises the addition of one or more excipients before and / or after the granulation step, which may be binders, diluents, disintegrants, lubricants, glidants , dyes, conventional odor modifiers used for the preparation of solid galenic forms.

Thus, for example, micronized fenofibrate may be mixed with one or more binders such as e.g. starch, pregelatinized starch, sugars (lactose) •

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9, glucose, dextrose and the like), polyvinylpyrrolidinone, methylcellulose, ethylcellulose, carboxymethylcellulose or microcrystalline cellulose, and / or with one or more diluents such as e.g. lactose, kaolin, mannitol, starch, sodium chloride, calcium phosphate, and / or with one or more disintegrating ingredients - starch, sodium carboxymethyl starch, chalk, carboxymethylcellulose or alginic acid. It may prove advantageous to add one or more lubricants, such as e.g. magnesium stearate, calcium stearate or talc, starches, cellulose and its derivatives and / or one or more glidants - colloidal quartz, magnesium stearate, sodium carboxymethyl starch, calcium phosphate, granulated mannitol or microcrystalline cellulose, and / or one or more dyes or modifiers fragrance, depending on the desired consistency of the galenic form as well as the intended processing (filling into gelatin capsules, compression into tablets, etc.).

According to another aspect of the present invention, the invention further comprises adjusting the particle size of the granulate after drying and before optionally mixing it with one or more excipients. Adjustment of the particle size of the granulate is performed under suitable conditions to allow removal of all granules with a size equal to or greater than 150 µm.

In accordance with a further preferred claim of the present method, the subject matter of the invention further consists in that the micronization of fenofibrate is carried out so that the process results in a powder whose particles have a homogeneous size not greater than 10 µm, preferably between 5 and 10 µm.

In accordance with another preferred claim of the present method, the subject matter of the invention is that the particles resulting from the micronization of fenofibrate should have a specific surface area of between 0.7 to 1.6 m / g, preferably about 1 m / g.

The inventors have observed, but without being able to justify their observation, that micronizing fenofibrate under the same conditions produces particles with different surface areas depending on the production method by which micronized fenofibrate was prepared, with identical physical properties: density, porosity (measured as pore diameter from 1 to 100 nm), melting point, absence of polymorphism, crystalline system. This difference in the specific surface area correlates with the measure

-6 · · · φ · · · · · • · φ · Φ · Φ · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Excitation energy, which is also different, but to a lesser extent (individual specific excitation energies expressed in J / kg differ by about 10-20%). In addition, the inventors have found that while the wettability of the fenofibrate particles or the fenofibrate / excipient mixture by the liquid medium during granulation (the wettability of the granulation process and thus the quality of the granulate obtained) is higher in the presence of alcohol in the medium, this effect is even more pronounced have a surface area of between 0.7 and 1.6 m / g, preferably about 1 m ² / g.

According to the invention, the surfactant is present in the liquid medium used in the granules at a molar concentration ranging from 0.1 to 1, preferably between 0.2 to 0.5, the ratio between the volume of water and alcohol in the same medium being between 0.25 to 4, preferably between 0.5 to 2. The water / alcohol volume ratio is preferably selected according to the surface area of the particles resulting from the micronization of fenofibrate. It has been found that, in order to achieve granulation of a certain quality, it is generally necessary to use a water / alcohol volume ratio which is all the greater the higher the surface area of the fenofibrate particles. Conversely, the lower the surface area of the particles, the lower the volume ratio mentioned.

According to a further preferred claim of the present method, the present invention is characterized in that the weight of the liquid medium used in the granules is between 5 and 70%, preferably between 15 and 50% by weight of the fenofibrate particles or the mixture of fenofibrate particles and excipient subjected to the granules.

Preferably, sodium surfactant is used as surfactant and ethanol is miscible with water. However, other surfactants such as e.g. sodium dioctylsulfosuccinate, sodium dodecylbenzenesulfonate, quaternary ammonium halides, polysorbates and ethers of aliphatic alcohols and polyethylene glycol. In the process of the present invention, e.g. isopropanol.

According to a particularly preferred method of the present invention, the present invention is based on:

(a) micronizing fenofibrate;

(b) mixing the micronized fenofibrate with one or more binders and / or diluents and / or disintegrants;

-7 · e c c c c c c c c c c c c c c c c preparing a liquid medium to be granulated by dissolving sodium lauryl sulfate in a solution of water and alcohol;

(d) granulating the mixture obtained in step (b) in the presence of the described liquid medium;

(e) drying the granulate thus obtained;

(f) adjusting the particle size of the granulate so obtained; and (g) mixing the granulate so obtained with one or more lubricants and / or glidants and / or colorants and / or fragrance modifiers.

The process for preparing the galenic form object of the present invention has many advantages. The method makes it possible to produce a galenic form of fenofibrate with high bioavailability of fenofibrate and thereby reduce the dose of fenofibrate required to achieve a therapeutic effect compared to currently recommended dosage regimens (as will be demonstrated later). It is also an advantage that by incorporating the surfactant directly into the liquid medium used in the fenofibrate granules, the present process comprises one step less than other currently used methods for producing the fenofibrate formulations. This allows for better reproducibility of production runs and significant cost savings. In addition, the present process does not require special devices and can be easily accomplished using devices commonly available in laboratories equipped for the preparation of medicaments in solid form, in particular for granulating the active ingredients in a liquid medium.

The present invention also provides a galenic form comprising fenofibrate as an active ingredient, characterized in that it is prepared as defined above.

The present invention also provides a medicament for oral administration, characterized in that it comprises an effective amount of the galenic form obtained as defined above.

The invention encompasses a preferred particular form of medicament made in the form of gelatin capsules, preferably made of gelatin. Under such conditions, it may be prepared by a process comprising filling a gelatin capsule of appropriate size with a predetermined amount of the galenic form of the present invention.

However, a medicament in the form of uncoated or coated (film-coated) tablets may also be prepared as a variant. These are prepared by molding the galenic form prepared according to the present invention. If desired, the tablets obtained by compressing the galenic form are film-coated.

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As another particular embodiment of the disclosed medicament, the invention encompasses a fenofibrate dose of 100 to 200 mg per therapeutic unit administered once daily.

It is also an object of the present invention to use a liquid medium containing a surfactant, water and a water miscible alcohol to granulate fenofibrate or a mixture comprising fenofibrate and one or more excipients.

It is also an object of the present invention to use fenofibrate particles, o

having a surface area of between 0.7 to 1.6 m / g, preferably about 1 m / g, for the preparation of a medicament for oral administration.

Overview of the figures in the drawing

In FIG. 1 is a graph illustrating mean plasma concentrations of fenofibric acid expressed in pg / ml plasma.

DETAILED DESCRIPTION OF THE INVENTION

In addition to the foregoing claims, the invention also encompasses other characteristics that will emerge from the following description, which addresses examples of drug preparation in accordance with the present invention, examples demonstrating their pharmacokinetics as well as FIG. 1, which shows mean plasma concentrations of fenofibric acid expressed in pg / ml plasma. Values were obtained from healthy subjects after administration of the drug in accordance with the present invention (20 minutes after standard breakfast) as a gelatin capsule with a 200 mg dose of fenofibrate (♦) or after administration of 3 SECALIP® 100 gelatin capsules (A) under the same conditions.

It should be understood, however, that these examples are given merely to illustrate the subject matter of the invention and should not in any way limit its scope.

Example 1

Preparation of a medicinal product supplied as gelatin capsules containing 150 mg fenofibrate. Gelatin capsules are prepared so that each has the following

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quantitative and qualitative composition: fenofibrate 150.0 mg (specific surface area after micronization 0.80 - 0.85 m ² / g) lactose monohydrate 25.9 mg microcrystalline cellulose 13.5 mg povidone 5,2 mg sodium carboxymethyl starch 16.8 mg sodium lauryl sulfate 4.5 mg magnesium stearate 2.2 mg the preparation was carried out as follows:

- fenofibrate is micronized in an air-jet apparatus to obtain a powder containing particles having a homogeneous size of 5-10 µm and whose surface area, measured by conventional BET gas adsorption technique (ADSORPTION SURFACE AREA AND POROSITY, 1982) , SJGREGG and KSW SING, ACADEMIC PRESS) is between 0.80 and 0.85 m ² / g;

this powder is mixed with lactose monohydrate, povidone, microcrystalline cellulose and 2/3 (by weight) of sodium carboxymethyl starch;

- granulation of the resulting mixture is carried out in the presence of a solution of water and alcohol (distilled water / ethanol, 60/40 v / v), the weight of the solution being 23% by weight of the mixture used. The alcohol / water mixture contains 0.23 mol / liter sodium lauryl sulfate;

- the granules thus obtained are subjected to drying for 10 hours at a temperature of 55 ° C and subsequently selected by size so that only granules less than or equal to 150 µm remain;

- the magnesium stearate and the remainder of the sodium carboxymethyl starch are added to the granules, mixed until a homogeneous powder is obtained, and

- the powder is filled with size 1 gelatin capsules so that each capsule contains 218.2 mg of powder.

Example 2

Drug preparation in the form of gelatin capsules containing 200 mg fenofibrate.

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Gelatin capsules are prepared so that each has the following

quantitative and qualitative composition: fenofibrate 200 mg (specific surface area after micronization: 1.38 - 1.50 m ² / g) lactose monohydrate 50 mg povidone 7 mg pregelatinized starch 30 mg sodium lauryl sulfate 6 mg magnesium stearate 4.5 mg anhydrous colloidal quartz 1.5 mg the preparation was carried out as follows:

- fenofibrate is micronized in an air-jet apparatus to obtain a powder containing particles of 5-10 µm homogeneous size and whose surface area measured by conventional BET gas adsorption technique is from 1,38 to 1, 50 m ² / g;

- the powder thus obtained is mixed with lactose monohydrate, povidone and pregelatinized starch;

- granulation of the resulting mixture is carried out in the presence of a solution of water and alcohol (distilled water / ethanol, 60/40, v / v), the weight of the solution being 17% by weight of the mixture used. The alcohol / water solution contains 0.38 mol / liter sodium lauryl sulfate;

the granules so obtained are dried and selected according to size as described in Example 1;

- magnesium stearate and anhydrous colloidal quartz are added to the granules and mixed until a homogeneous powder is obtained;

- the powder is filled with size 1 gelatin capsules so that each capsule contains 299 mg of powder.

Example 3

Pharmacokinetic Study of the Medicament of the Invention The pharmacokinetic study of the medicament of the present invention is as follows: < tb > ______________________________________ < tb > · · · · 9 9 9 9 ·· ·· · ·· ·

The increased bioavailability of fenofibrate when administered in the galenical form prepared according to the present invention has been confirmed by a scientific study comparing the pharmacokinetic profile of the drug prepared according to the present invention - i. a pharmaceutical containing the galenical form prepared according to the present invention - with the profile of a reference medicine containing fenofibrate, in this case SECALIP® 100, which, as mentioned above, replaced LIPANTHYL® 100 on the French market after 1991.

In this cross-over clinical study, 18 healthy volunteers 21 to 31 years of age were treated orally with 1 gelatin capsule containing 200 mg fenofibrate prepared as described in Example 2 (hereafter referred to as therapy A) and 3 gelatin. SECALIP® 100 capsules in a single dose (hereinafter referred to as therapy B).

The order of the therapies (i.e., whether the proband first underwent therapy A and then therapy B or vice versa) was determined by random selection. A 14 day interval was maintained between therapies to ensure reliable elimination of fenofibric acid from the first therapy by the second therapy date.

In all cases, the capsules were administered 20 minutes after the standard breakfast. Blood samples for fenofibric acid plasma levels were taken before drug administration and then 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours after drug administration. After immediate centrifugation of the sample, plasma was separated and stored at -20 ° C until the plasma level of fenofibric acid was determined. The determination was performed by high performance liquid chromatography.

For all probands, the following pharmacokinetic parameters were separately determined for each therapy:

- maximum plasma concentration of fenofibric acid (C _max ) achieved,

- time at which the maximum concentration (T _max ) was reached,

- the area under the curve of the graph showing the plasma concentration of fenofibric acid as a function of time (AUC 0-t), and

- the area under the graph showing the plasma concentration of fenofibric acid as a function of time, extrapolated to infinity (AUC 0 _-a )

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Table 1 shows the mean values and standard deviations of the determined pharmacokinetic parameters.

Table 1

therapy A therapy B Cmax (pg / ml) 9.36 ± 3.41 3.80 ± 1.52 Tmax (h) 4.4 ± 1.3 5.3 ± 2 AUC 0-t (pg / ml hr) 143 ± 73 84.2 ± 45.9 AUCo-α (pg / ml hr) 148 ± 74 92.5 ± 46.2

Fig. 1 illustrates the mean plasma concentrations of fenofibric acid expressed in pg / ml plasma, which were determined within 120 hours of treatment A (♦) and treatment B (A).

The results shown in Table 1 and FIG. 1 show that for therapy A:

- on the one hand, the amount of fenofibrate absorbed is much higher. Not only is the peak (peak) concentration of fenofibric acid (C _{m and} x) approximately twice as high as for therapy B (2.4-fold according to Table 1 and 2.16-fold according to Figure 1), but at the same time the areas are below the graph curves showing plasma concentrations of fenofibric acid as a function of time (AUCo- _t and AUCo-α) significantly greater than those observed with therapy B, and

on the other hand, fenofibrate is absorbed as quickly as in the case of therapy B, because according to Table 1, the concentration peak for therapy A is reached an average of one hour earlier than for therapy B. According to FIG. 1, concentration peaks are achieved at approximately the same time for both therapies, although the dose of fenofibrate administered in therapy A is lower than the amount administered in therapy B (200 mg versus 3 x 100 mg).

In addition, since it has been shown that in terms of biological kinetics, 3 SECALIP® 100 gelatin capsules (which replaced LIPANTHYL® 100) equivalent to 1 LIPANTHYL® 200 Micronisé gelatin capsule, results shown in

- 13 · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Table 1 and FIG. 1 means that the galenic form prepared in accordance with the present invention and containing 200 mg of fenofibrate will provide faster and more complete intestinal absorption than the LIPANTHYL® 200 mg gelatin capsule - a fenofibrate formulation showing the best efficacy and dose ratio so far. The galenical form of the present invention allows the same therapeutic effect to be achieved when the drug is administered once every 24 hours at a dose of less than 200 mg.

The galenical form of the present invention allows for the preparation of medicaments with a lower risk of adverse effects, greater patient comfort and improved patient compliance with long-term treatment with fenofibrate.

As is apparent from the foregoing, the scope of the present invention is not limited to its implementations, applications, and particular formulations, which have been explicitly described herein. The invention also encompasses all variants of the foregoing that one skilled in the art may encounter within the structure and scope of the present invention.

Claims (9)

PATENT CLAIMS 1. A process for the preparation of novel galenic forms of fenofibrate, characterized in that: A) micronization of fenofibrate (b) fenofibrate granules in the presence of a liquid medium containing surfactant, water and water miscible with water; and c) drying the granulate thus obtained. The process according to claim 1, characterized by the addition of one or more excipients belonging to binders, diluents, disintegrants, lubricants, glidants, colorants or odor modifiers, before and / or after the granulation process. Preparation process according to claim 1 or 2, characterized in that the particle size of the granulate is adjusted after drying of the granulate and before its possible mixing with one or more excipients. Method according to one of Claims 1 to 3, characterized in that the micronization of fenofibrate is carried out by a process which makes it possible to obtain a powder whose particles are homogeneous in size and whose size does not exceed 10 μτη, preferably between 5 and 10 µm. Preparation process according to one of claims 1 to 4, characterized in that the particles resulting from the micronization of fenofibrate have a specific surface area of between 0.7 to 1.6 m ² / g, preferably about 1 m ² / g. Preparation process according to any one of claims 1 to 5, characterized in that the liquid medium used for granulation contains the surfactant in a molar concentration of from 0.1 to 1, preferably between 0.2 to 0.5. Preparation process according to any one of claims 1 to 6, characterized in that the liquid medium used for granulation comprises water and alcohol in a volume ratio of 0.25 to 4, preferably between 0.5 to 2. -15 ································· I 8th 9th 11th Process according to any one of claims 1 to 7, characterized in that the weight of the liquid medium used for granulation is between 5 and 70%, preferably between 15 and 50% by weight of the fenofibrate particles or of the mixture of fenofibrate particles and the excipient (s) granulation. The process according to any one of claims 1 to 8, wherein the surfactant is sodium lauryl sulfate. The method of any one of claims 1 to 9, wherein the water miscible alcohol is ethanol. Process according to any one of claims 1 to 10, characterized in that: (a) micronisation of fenofibrate, b) mixing the micronized fenofibrate with one or more binders and / or diluents and / or disintegrants, c) preparing a liquid medium used in granulation, which is prepared by dissolving sodium lauryl sulfate in an aqueous-alcohol solution, d) granulating the mixture obtained in step b) in the presence of the described liquid medium, e) drying the granulate thus obtained, f) adjusting the particle size of the granulate, g) mixing said granulate with one or more lubricants and / or glidants and / or colorants and / or fragrance modifiers. Galenic form comprising fenofibrate as active ingredient, characterized in that it has been prepared by a process according to any one of claims 1 to 11. A medicament for oral administration comprising an effective amount of the galenic form obtained by the method of any one of claims 1 to 11. Medicament according to claim 13, characterized in that it is produced in the form of gelatin capsules, preferably made of gelatin. ·· • · · -16 ·· ··························· Medicament according to claim 13 or 14, characterized in that it contains fenofibrate in an amount of between 100 and 200 mg per therapeutic unit, wherein one therapeutic unit per day is administered. Use of a liquid medium containing surfactant, water and a water miscible alcohol for granulating fenofibrate or a mixture containing fenofibrate and one or more excipients. Use of fenofibrate particles having a specific surface area of between 0.7 to 1.6 m / g, preferably about 1 m / g, for the preparation of a medicament for oral administration