KR20110031889A - Solid dispersant comprising fibrates and a method for preparing the same - Google Patents

Abstract

PURPOSE: A solid dispersion containing fibrate drugs is provided to improve elution rate and bioavailability and to have sample drug efficiency using a small amount of the drug. CONSTITUTION: A solid dispersion of fibrate drugs is prepared by heat-melting fibrate drugs, polymer melting substrate, surfactant, and polymer solubilizing agent. The ratio of the polymer melting substrate with respect to the fibrate drugs is 1:0.1-1:3. A pharmaceutical composition for treating hyperlipidemia contains the solid dispersion as an active ingredient. A method for manufacturing the solid dispersion comprises: a step of melting the fibrate drugs, polymer melting substrate, surfactant, and polymer solubilizing agent at 50-150°C to form a polymeric melted mixture; a step of cooling the mixture at 15-30°C to solidify; and a step of pulverizing the mixture to prepare fine particles.

Description

Solid dispersant comprising fibrate-based drug and a method for preparing the same {Solid dispersant comprising fibrates and a method for preparing the same}

The present invention relates to a solid dispersion of a fibrate-based drug prepared using a heat melting process and a method for preparing the same. More specifically, the present invention, in order to improve the bioavailability of the fibrate-based drug used in the treatment of hyperlipidemia, to form a molten mixture by heat melting the fibrate-based drug, polymer melt base, surfactant and polymer solubilizer, The present invention relates to a solid dispersion of a fibrate-based drug obtained by cooling, solidifying and pulverizing, and a method for producing the same.

Due to the remarkable development of pharmacy, various high performance new drugs are being developed. However, many drugs that are developed are extremely limited in clinical use due to their low solubility.

In order to improve the dissolution rate of such poorly soluble drugs, there is a method of increasing the solubility of poorly soluble drugs through chemical or physical modification of the drug. Common methods for chemical modification include salt attachment and water soluble prodrugs, and common methods for physical modification include particle size, crystalline modification, crystal polymorph formation, complex formation with surfactants or cyclodextrins, and drug dispersion through dispersants. There is a law. In particular, in order to increase the solubility and absorption of the drug, various formulation methods have been proposed, such as drug miniaturization, amorphous, solid dispersion.

Among these, solid dispersion has been widely studied as a method for dispersing a drug in an inert carrier.

Although some methods are proposed as a manufacturing method of a solid dispersion, the solvent method is mentioned as a method generally used. The solvent method is a method of preparing a solid dispersion by dissolving a drug and a water-soluble polymer in a carrier in a solvent such as an organic solvent and then distilling off the solvent, or dissolving the drug in a solvent to disperse in the carrier and then distilling off the solvent. .

Japanese Patent Publication No. 3-1288 and Japanese Patent No. 3028404, which are prior art documents on the solvent method, are fine granules obtained by assembling lactose with a water-soluble polymer such as hydroxypropyl cellulose. A solid dispersion obtained by spraying and drying a liquid obtained by dissolving a polymer base such as vinylpyrrolidone, hydroxymethyl cellulose or methyl cellulose in an organic solvent is disclosed.

WO 01/80828, on the other hand, discloses a process for preparing a mixture of a drug and at least one surfactant, heating the mixture to the melting point or higher of the poorly soluble drug, and then homogenizing the heated suspension. However, the process of obtaining the final formulation is complicated and there is a fear that the drug may be recrystallized by homogenization in water.

In particular, 2- [4- (4-chlorobenzoyl) phenoxy] -2-methyl-propanoic acid, 1-methelethyl ester (hereinafter referred to as 'fenofibrate'), which is one of the fibrate drugs that are widely used in the treatment of hyperlipidemia, which is widely used worldwide. ) Is a poorly soluble drug that is insoluble in water. Therefore, the oral administration of fenofibrate has a low dissolution rate due to the rapid drug release, and thus has a problem of low bioavailability, many efforts have been made to improve the bioavailability of the fenofibrate formulation.

Some of these attempt to improve bioavailability using emulsions and suspensions of fenofibrate, while others disclose specific polymer or surfactant additives and micronized fenofibrate formulations.

For example, US Pat. Nos. 4,895,726 and 5,880,148 disclose co-micronized fenofibrate with a surfactant, and US Patent Application Publication No. 20030224059 discloses microparticles of pharmaceutically active ingredients, including Drug delivery vehicles and methods for their preparation are disclosed.

The refinement of fenofibrate and the combination of micronized fenofibrate and surfactant have the advantage of increasing the bioavailability of fenofibrate to some extent, thus reducing the amount administered, although the bioavailability in the fed state is the same. However, there is room for improvement since the actual bioavailability of fenofibrate is still low and can be toxic with the use of surfactants that are harmful to the human body.

Therefore, there is a need for the development of a technique for more efficiently improving the bioavailability of the fibrate-based drug, which is a drug used in the treatment of hyperlipidemia, in a safe manner.

Accordingly, the present inventors have endeavored to find the optimal process conditions for preparing solid dispersions in consideration of the specificity that the fibrate-based drug has a relatively low melting point. As a result, the fibrate-based drug, the polymer melt base, the surfactant, and the polymer When the solubilizer is melted by heat (hot melt) to prepare a solid dispersion of the amorphous fibrate-based drug, the dissolution rate and bioavailability are remarkably improved compared to the conventional spray drying method, so that even when a small amount of drug is administered, an equivalent drug can be obtained. And the present invention was completed.

The solid dispersion according to the heat melting method of the present invention has the following advantages over the spray drying method. The spray drying method must use high pressure and must use organic solvents, so it can be harmful to human body such as workers, environmental pollution, and organic solvents may remain in the final product. In addition, the spray-dried body prepared by the spray drying method is too large to be difficult to formulate, and the process of smashing for the reduction of the volume is required. However, the hot melt solid dispersion according to the present invention does not use the organic solvent, there is no problem caused by the use of the organic solvent as described above, the volume of the powder is easy to handle and the molten composition is filled in the capsule It has the advantage of being able to make a product by making or tableting.

The present invention is to improve the dissolution rate and bioavailability of fibrate, a poorly soluble drug, by providing a solid dispersion of the fibrate-based drug obtained by thermal melting of the fibrate-based drug, a polymer melting base, a surfactant and a polymer solubilizer. .

In addition, the present invention is to provide a method for producing a solid dispersion of the fibrate-based drug by a heat melting method.

The present invention provides a solid dispersion of a fibrate drug obtained by thermal melting a fibrate drug, a polymer melting base, a surfactant, and a polymer solubilizer.

Another aspect of the present invention comprises the steps of melting a fibrate-based drug, a polymer melt base, a surfactant and a polymer solubilizer at 50 to 150 ℃ to form a polymer melt mixture; Cooling the polymer melt mixture to 15 to 30 ° C. to solidify the molten polymer; And to provide a method for producing a solid dispersion of the fibrate-based drug comprising the step of preparing the fine particles by grinding the solidified polymer mixture.

The present invention also provides a pharmaceutical composition for treating hyperlipidemia, which comprises a solid dispersion of a fibrate drug obtained by thermal melting a fibrate drug, a polymer melting base, a surfactant, and a polymer solubilizer.

The solid dispersion of the fibrate-based drug according to the present invention has a remarkably improved dissolution rate and bioavailability compared to the fenofibrate preparation prepared by the conventional spray drying method, so that even when a small amount of drug is administered, an equivalent drug can be obtained.

In addition, the solid dispersion manufacturing method according to the present invention is a simple process and does not require a separate equipment is not only an economical process, there is no fear that the organic solvent remains in the final product because the organic solvent is not used in the chemical manufacturing step It is an environmentally friendly and bio-friendly manufacturing process with no possibility of environmental pollution by organic solvents.

1 is a SEM photograph of the solid dispersion of Example 1.
FIG. 2 is a DSC analysis result of the solid dispersion of Example 1 and control sample 1 (lipidyl supra® tablets) based on control sample 2 (crystalline fenofibrate). FIG.
3 is a graph of drug dissolution rate with time obtained as a result of the dissolution test according to Test Example 1.
4 is a graph of drug dissolution rate with time obtained as a result of the dissolution test according to Test Example 2.
5 is a graph of drug dissolution rate with time obtained as a result of the dissolution test according to Test Example 3.
6 is a graph showing blood drug concentrations measured after drug administration according to Test Example 4.

The present invention provides a solid dispersion of a fibrate-based drug comprising a fibrate-based drug, a polymer melt base, a surfactant, and a polymer solubilizer. Specifically, the present invention provides a solid dispersion of a fibrate drug obtained by thermal melting a fibrate drug, a polymer melt base, a surfactant, and a polymer solubilizer.

Fibrate Drug

In the present specification, the fibrate-based drug includes fenofibrate known to exhibit a hyperlipidemic effect, fenofibric acid ester, fenofibric acid, benzafibrate, binifibrate, clinofibrate, and sif Ciprofibrate, clofibrate, clofibride, clofibride, etofibrate, etophylline clofibrate, gemfibrozil, pyrifibrate ), Ronifibrate, simfirate, or a pharmaceutically acceptable salt thereof.

Polymer Melt Base

In order to improve the dissolution of the drug by preparing a solid dispersion of poorly soluble drugs such as fibrate-based drugs, it is important to determine the type and content ratio of the carrier that can maintain the dissolution rate at the absorption site of the drug. . The present invention prepares a solid dispersion by melting the fibrate-based drug and the polymer melt base with heat so that the fibrate-based drug is eluted in a large amount in the intestinal tract absorption.

Examples of the polymer melt base include polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone vinyl acetate copolymer, polyvinyl alcohol, polyacrylic acid polymer, and the like, and preferably polyethylene glycol. The average molecular weight of the polymer melt base is 2,000 to 10,000 Daltons, preferably 4,000 to 8,000 Daltons. The molten base helps the melting of the drug to be uniformly mixed in the oil phase, and serves as an absorption improvement base.

The weight ratio of the fibrate drug and the polymer melt base may be in the range of 1: 0.1 to 1: 3, preferably 1: 0.5 to 1: 2. If the weight ratio of the polymer melt base to the drug exceeds 3, it is unsuitable for formulation due to the sticky surface properties, and if less than 0.1, there is no effect of improving the bioavailability of the drug.

Surfactants

The surfactant of the present invention is a polymer surfactant, preferably poloxamer, alpha tocopheryl polyethylene glycol succinate, polyoxyl 40 stearate, polysorbate, sodium lauryl One or more mixtures selected from the group consisting of sulfate, docusate sodium. More preferably poloxamer. Since the surfactant of the present invention mediates the bond between the amorphous fibrate-based drug produced after melting and cooling and the polymer melt base, the surfactant and the polymer melt base serve to increase the dissolution of the fibrate-based drug. In the embodiment of the present invention, the poloxamer may have a HLB value of 20 to 30, and preferably poloxamer 188, 407, and the like.

The weight ratio of the fibrate-based drug and the surfactant may range from 1: 0.1 to 1: 5, preferably 1: 1 to 1: 3. If the ratio of the surfactant to the drug is less than 0.1, there is no effect of improving the bioavailability of the drug, and if it exceeds 5, the dosage of the agent is increased, which causes problems in formulation.

In a preferred embodiment, the weight ratio of polymer melt base and surfactant is 10: 1 to 1:10, more preferably 2: 1 to 1: 2.

Polymer solubilizer

The polymer solubilizer according to the present invention preferably has a melting temperature of 40 to 60 ° C and a glass transition temperature of 100 to 200 ° C. Specifically, it is hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), etc., Preferably it is HPMC. When the polymer melt base and the polymer solubilizer are used as the base at the same time, the solubilizer is dissolved in the polymer melt base to maximize the solubility of the drug than when the polymer melt base alone. Examples of HPMC according to the present invention include HPMC 2910, 2906, 2208, 1828 and the like. The weight ratio of the fibrate drug and the polymer solubilizing agent may be in the range of 1: 0.1 to 1: 2, preferably 1: 0.5 to 1: 2. If the weight ratio of the polymer solubilizer is greater than 2, the amount of the polymer solubilizer is too large to produce a melt mixture, and if it is less than 0.1, there is no solubility improvement effect.

The polymer solubilizing agent of the present invention is included to increase the solubility of the solid dispersion, and may be included in the solid dispersion by melting and cooling with the fibrate-based drug.

In preparing the solid dispersion according to the present invention, the dissolution rate of the drug may be controlled by appropriately adjusting the type and content of the polymer melt agent, the surfactant, and the polymer solubilizer. As the content of the surfactant and the polymer solubilizing agent increases, the dissolution rate of the drug increases, but it is preferable not to exceed 10 times the weight of the fibrate-based drug in consideration of one dose.

The size and shape of the solid dispersion according to the present invention is not particularly limited, but is in the form of fine particles of 10 to 1,000 um, more preferably 500 to 800 um, more preferably 300 to 800 um.

In one embodiment of the invention the most preferred weight ratio of fibrate-based drug: polymer melt base: surfactant: polymer solubilizer is 1: 1: 2: 1.

Another aspect of the present invention is the homogeneous melting of the fibrate-based drug, the polymer melt base, the surfactant and the polymer solubilizer by melting under 50 to 150 ℃, preferably 80 to 120 ℃, more preferably 80 to 100 ℃ Forming a mixture; Cooling the polymer melt mixture to 15 to 30 ° C. to solidify the molten polymer; And to provide a method for producing a solid dispersion of the fibrate-based drug comprising the step of preparing the fine particles by grinding the solidified polymer mixture. The drug, the polymer melt base, the surfactant and the polymer solubilizer may be melted simultaneously after mixing, or separately in any order.

In a preferred embodiment, 20 to 60 parts by weight of a surfactant such as poloxamer and 10 to 40 parts by weight of polyethylene glycol are mixed and melted under stirring at 80 to 100 ° C., followed by addition of 10 to 40 parts by weight of hydroxypropylmethylcellulose. While homogenizing, 20 parts by weight of the fibrate-based drug was added thereto, melted with stirring, cooled, and pulverized into fine particles to prepare a solid dispersion.

The present invention also provides a pharmaceutical composition for treating hyperlipidemia comprising a solid dispersion of a fibrate drug obtained by thermal melting of a fibrate drug, a polymer melting base, a surfactant, and a polymer solubilizer.

The solid dispersion of the fibrate-based drug according to the present invention has a markedly improved dissolution rate and bioavailability, so that even when a small amount of drug is administered, an equivalent drug can be obtained.

In one embodiment of the present invention, the solid dispersion obtained by thermal melting of the fibrate-based drug, polymer melt base, surfactant, polymer solubilizing agent is to be tested for dissolution according to the second method (100 rpm) When at least 80% by weight of the drug elutes within 30 minutes.

More specifically, the solid dispersion according to the present invention, when measuring the dissolution rate by the 9th Amendment 2 method (paddle method, rotation speed 100rpm) of the pharmacopeia, 30% by weight or more of the fibrate-based drug within 15 minutes, 15 More than 60% by weight of the drug within minutes, 80% by weight or more of the drug within 30 minutes has a dissolution pattern that is dissolved. Preferably, the present invention, when measuring the dissolution rate by the 9th Amendment 2 method (paddle method, rotation speed 100rpm) of the pharmacopeia, 50% by weight or more of the fibrate-based drug within 5 minutes, 80 of the drug within 15 minutes Provided is a solid dispersion having an elution pattern in which at least 95% by weight of the drug is dissolved within 30% by weight or more.

The solid dispersions or pharmaceutical compositions according to the invention are selected from pharmaceutically acceptable surfactants, preservatives, complexes, electrolytes, diluents, disintegrants, binders, lubricants, glidants, sweeteners, flavoring agents, and coloring agents as necessary. It may further include one or more kinds, and may further include an antihypertensive agent, an antihyperlipidemic agent and the like as other active ingredients. Any of the above components can be added during formulation of the solid dispersion of the present invention or after preparation.

Solid dispersions or pharmaceutical compositions of the fibrate-based drugs prepared according to the present invention may be formulated into pharmaceutical preparations containing a therapeutically effective amount of the drug. For example, it may be prepared as an oral dosage form such as tablets, capsules, granules and dry syrups, eye drops, nasal sprays or inhaled pharmaceutical compositions. In determining the ease of use and commerciality of the license, tablet formulations, more preferably tablets by direct method, are most preferred, in which case they can be prepared by excipients and manufacturing techniques for conventional tablet formulations. Oral dosage forms formed into tablets can be prepared by conventional tablet preparation techniques, including conventional ingredients or excipients, including surfactants, preservatives, complexes, electrolytes, diluents, disintegrants, binders, lubricants, glidants, Sweetening, flavoring or coloring agents may be further included. In addition, tablets may be film-coated for the purpose of improving stability, flavor, ease of taking, appearance, and the like.

The dosage and frequency of administration of the pharmaceutical composition according to the present invention can be adjusted in consideration of factors such as the age, condition, weight of the patient, the severity of the disease to be treated.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to Examples.

Example

Example  One

20 g of polyethylene glycol 6000 (Macrogol 6000, Sanyo chemical industries, Japan) and 40 g of poloxamer 188 (Lutrol F68, BASF, Germany) were placed in a beaker, heated to about 90 ° C., dissolved by stirring, and mixed. After complete melting, 20 g of hydroxypropylmethyl cellulose 2910 (Pharmacoat 606, ShinEtsu, Japan) was added to the preceding melt and stirred to make it uniform. 20 g of fenofibrate was added thereto and stirred and melted. After complete melting and mixing, the mixture was spread out in a separate container for 4 hours and cooled to room temperature.

The solidified mass was crushed to a suitable size and pulverized into fine particles using ERWEKA AR402 (ERWEKA GmbH, Germany) equipped with 800um stainless steel sieve to obtain a solid dispersion.

The obtained solid dispersion was observed using a scanning electron microscope (SEM, model name: FE-SEM: Jeol (Japan) / JSM-6335F) (Fig. 1).

Example  2

Except that 10 g of hydroxypropyl methyl cellulose was used, the fine particles were obtained by the same ingredients and processes as in Example 1.

Example  3

Fine particles were obtained by the same ingredients and processes as in Example 1 except that 4 g of hydroxypropylmethylcellulose was used.

Example  4

20 g polyethylene glycol 4000 (Macrogol 6000, Sanyo chemical industries, Japan), 20 g poloxamer 188 (Lutrol F68, BASF, Germany), 10 g hydroxypropylmethylcellulose 2910 (Pharmacoat 606, ShinEtsu, Japan) and 20 g fenofibrate are placed in a beaker Mix while heating to about 90 ° C. After complete melting and mixing, the mixture was spread out in a separate container for 4 hours and cooled to room temperature.

The solidified mass was crushed to a suitable size and pulverized into fine particles using ERWEKA AR402 (ERWEKA GmbH, Germany) equipped with 800um stainless steel sieve to obtain a solid dispersion.

Comparative example  One

Fine particles were obtained by the same ingredients and processes as in Example 1 except that hydroxypropylmethylcellulose was not added.

Comparative example  2

Fine particles were obtained by the same ingredients and processes as in Example 1, except that poloxamer and hydroxypropylmethylcellulose were not added.

Comparative example  3

10 g of fenofibrate and 10 g of hydroxypropylmethylcellulose (HPMC) were placed in a beaker and heated but carbonized without melting. Therefore, when only HPMC was used, no solid dispersion was obtained.

Comparative example  4

20 g of lauroyl macrogolglycerides were placed in a beaker, heated to about 80 ° C., and dissolved with stirring. After melting completely, 20 g of fenofibrate was added thereto, followed by stirring and melting. After complete melting and mixing, they were spread out in a separate container and cooled.

Even when left at room temperature, they did not solidify and remained in the liquid phase and could not be made into fine particles.

Test Example  One

As a sample, the solid dispersion obtained in Example 1 was used, and Lipidyl Supra® tablet (Green Cross, South Korea) and crystalline fenofibrate (Dongdong FTL, South Korea), which are commercially available fenofibrate formulations, were used as Control Samples 1 and 2.

Samples and control samples were analyzed by differential scanning calorimetry (DSC) (model name: TA Instrument (USA) / DSC Q100, temperature conditions: 0 ℃ ~ 300 ℃) and the results are shown in FIG. From FIG. 2, Control Sample 1 (Lipidil Supra® Tablet) showed crystallinity as Control Sample 2 (crystalline fenofibrate), but it can be seen that the solid dispersion of Example 1 was present in an amorphous form.

In addition, the dissolution test was performed on the sample and the control sample under the following conditions, and the results are shown in Table 1 and FIG. 3.

Dissolution test conditions are as follows. The test method was the 9th amendment of the Korean Pharmacopoeia and the 2nd method (paddle method) and LABFINE Dissolution tester (LABFINE, Republic of Korea) was used as the dissolution apparatus. In 1000 mL of a 0.025 M solution of sodium lauryl sulfate (Sigma, USA), the temperature was maintained at 37 ± 0.5 ° C., and the dissolution behavior of each group was tested by rotating the paddle at 100 rpm.

Dissolution rate by weight (% by weight) Minutes 0 5 10 15 30 60 Control Sample 1 ¹⁾ 0 19.7 57.2 74.7 91.8 99.8 Control sample 2 ²⁾ 0 4.9 11.8 17 31.6 46.5 Example 1 0 58.7 84 93.7 98.3 100.0

1) Lipidyl Supra® Tablet

2) crystalline fenofibrate

While sample 2 (crystalline fenofibrate) showed a very low dissolution rate at a given dissolution condition, commercial control sample 1 (lipidyl supra® tablets) showed a relatively high dissolution rate, and the solid dispersion according to the invention Excellent dissolution rate and dissolution rate were shown.

Test Example  2

The dissolution test was performed on the samples obtained in Example 2, Comparative Examples 1 and 2 under the same conditions as in Test Example 1, and the results are shown in Table 2 and FIG. 4.

Dissolution rate by weight (% by weight) Minutes 0 5 10 15 30 Example 2 0 41.2 66.0 78.9 95.0 Comparative Example 1 0 29.8 47.0 57.0 82.2 Comparative Example 2 0 18.4 29.0 41.8 51.1

As shown in FIG. 4 and Table 2, the sample of Example 2 showed an excellent aspect in both dissolution rate and dissolution rate compared to the sample of Comparative Example 1 or 2.

Test Example  3

The dissolution test was performed on the samples obtained in Examples 1 to 3 under the same conditions as in Test Example 1, and the results are shown in Table 3 and FIG. 5.

Dissolution rate by weight (% by weight) Minutes 0 5 10 15 30 Example 1 0 58.7 84 93.7 98.3 Example 2 0 41.2 66.0 78.9 95.0 Example 3 0 32.0 49.0 61.1 83.0

According to the dissolution pattern shown in Table 3, it can be seen that the dissolution rate is greatly improved as the amount of hydroxypropylmethylcellulose used is increased.

Test Example  4

As a sample, the solid dispersion obtained in Example 1 was used, and Lipidyl Supra® tablet (Green Cross, South Korea), a fenofibrate formulation commercially available, was administered to white rats under the following conditions. of the body, pharmacokinetic variables in the metabolite fenofibrate of fenofibrate, AUC (Area Under Concentration) measured _{24 hr,} C _max (maximum concentration), and t _1/2 (half life), and table the results. 4 and FIG. 6 is shown.

-Experimental animals: Sprague-Dawley male rats (Charles River Laboratories (Orient, Korea))

Dosage: 50 mg / kg

Suspension in 1% CMC (High viscosity carboxymethylcellulose, Sigma, USA) solution orally administered.

Blood volume: 400 uL

Blood collection time: 30 minutes after administration, 1, 1.5, 2, 4, 6, 8, 24 hours

AUC _24hr (µg / hr / mL) C _max (μg / mL) t _1/2 (hr) Lipidyl Spra® Tablets 892.5 ± 184.9 66.3 ± 12.7 3.3 ± 2.3 Example 1 1246.8 ± 128.3 114.2 ± 34.1 3.3 ± 1.2

As shown in Table 4, in the case of Example 1 according to the present invention, since the AUC _24hr and Cmax increased by about 140% and 172%, respectively, compared to the conventional commercial control sample, it can be seen that the bioavailability was improved.

Claims (14)

A solid dispersion of a fibrate drug obtained by thermal melting a fibrate drug, a polymer melting base, a surfactant, and a polymer solubilizer. The method of claim 1, wherein the fibrate-based drug is fenofibrate, fenofibric acid ester, fenofibric acid, benzafibrate, binipibrate, clinfibrate, cipropibrate, clofibrate, clofibrid, etopi At least one solid dispersion selected from the group consisting of brates, etophylline clofibrate, gemfibrozil, pyrifibrate, ronifibrate, simfibrate, and pharmaceutically acceptable salts thereof. The method of claim 1, wherein the polymer melt base is one or two or more selected from the group consisting of polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone vinyl acetate copolymer, polyvinyl alcohol, and polyacrylic acid polymer, the average molecular weight Solid dispersion is a polymer of 2,000 to 10,000 Daltons. The solid dispersion of claim 1, wherein the weight ratio of the polymer melt base to the fibrate-based drug is from 1: 0.1 to 1: 3. The mixture of claim 1, wherein the surfactant is selected from the group consisting of poloxamer, alpha tocopheryl polyethylene glycol succinate, polyoxyl 40 stearate, polysorbate, sodium lauryl sulfate, and docusate sodium. Solid dispersion. The solid dispersion of claim 1, wherein the weight ratio of the surfactant to the fibrate-based drug is from 1: 0.1 to 1: 5. The solid according to claim 1, wherein the polymer solubilizing agent is hydroxypropylmethylcellulose (HPMC) or polyvinylpyrrolidone (PVP) having a melting temperature of 40 to 60 ° C and a glass transition temperature of 100 to 200 ° C. Dispersion. The solid dispersion of claim 1, wherein the weight ratio of the polymer solubilizer to the fibrate drug is from 1: 0.1 to 1: 2. The solid dispersion of claim 1, wherein the solid dispersion is fine particles having a size of 10 μm to 1,000 μm. Fibrate-based solid dispersion of fibrate-based drug obtained by thermal melting of fibrate-based drug, polymer melt base, surfactant, and polymer solubilizing agent. Solid dispersion in which at least 80% by weight of the drug is eluted. The method of claim 10, wherein the solid dispersion is at least 30% by weight of the fibrate-based drug within 5 minutes, 60% by weight or more of the fibrate-based drug within 15 minutes when the dissolution rate is measured by the KP method 2 (paddle method) , Solid dispersion having an elution pattern eluting at least 80% by weight of the fibrate-based drug within 30 minutes. A pharmaceutical composition for treating hyperlipidemia comprising the solid dispersion according to any one of claims 1 to 11 as an active ingredient. 13. The composition of claim 12, wherein the composition is at least one selected from the group consisting of pharmaceutically acceptable surfactants, preservatives, complexes, electrolytes, diluents, disintegrants, binders, lubricants, glidants, sweeteners, flavors, and colorants. A pharmaceutical composition further comprising an additive. Melting a fibrate-based drug, a polymer melt base, a surfactant, and a polymer solubilizer under 50 to 150 ° C. to form a polymer melt mixture; Cooling the polymer melt mixture to 15 to 30 ° C. to solidify the molten polymer; And pulverizing the solidified polymer mixture to produce microparticles.

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