KR20110046990A - Self-Microemulsifying Drug Delivery System Composition Containing Olmesartanmedoxomil and Method for Preparing the Same - Google Patents

Abstract

PURPOSE: A self-microemulsifying drug delivery system composition containing olmesartan medoxomil is provided to enable smooth absorption of active ingredients into the body. CONSTITUTION: A self-emulsifying drug delivery system of olmesartanmedoxomil contains 0.1-10 weight% of olmesartanmedoxomil, 5-60 weight% of oil, 20-90 weight% of surfactant, and 10-50 weight% of co-surfactant. The oil is fatty acid ester of propylene glycol. The fatty acid ester of propylene glycol is capryol 90(polyethyleneglycol monocarpylate). The surfactant is non-ionic surfactant. The non-ionic surfactant is castor oil, tweens, spans, or labrasols. The co-surfactant is diethylene glycolmonoethylether(transcutol) or tetraglycol.

Description

Self-Microemulsifying Drug Delivery System Composition Containing Olmesartanmedoxomil and Method for Preparing the Same}

The present invention relates to a composition for a self-emulsifying drug delivery system of olmesartan medoxomil and a method for preparing the same, more specifically olmesartanmedoxomil including olmesartan medoxomil, oils, surfactants and cosurfactants The present invention relates to a composition for self-emulsifying drug delivery system and a method of manufacturing the same.

Olmesartan medoxyl wheat is an angiotensin II antagonist that was approved in 2002 by the Food Drug Administration (FDA) for the treatment of hypertension. Olmesartanmedoxomil selectively inhibits the binding of angiotensin II to AT1 receptor angiotensin receptor in vascular smooth muscle, resulting in blood pressure such as vasoconstriction of angiotensin II, promoting synthesis and secretion of aldosterone, enhancing heart rate, and reabsorbing tubules of sodium Inhibit the synergy, the blood pressure is lowered. In particular, olmesartan methoxomile was randomized in 588 patients with mild or severe essential hypertension with existing angiotensin II antagonists, losartan, valsartan, and irbesartan. The multicenter, double-blind study showed that the diastolic blood pressure lowering effect after 8 weeks of olmesartanmedoxomil was superior to that of the other drug groups. The amount of change in blood pressure (mmHg) was 11.5 mmHg for olmesartan medoxyl wheat, 8.2 mmHg for losartan, 7.9 mmHg for valsartan, and 9.9 mmHg for ibsartan, 40% compared to Losartan, 46% compared to Valsartan, and Ivesar It was confirmed that the blood pressure drop difference of 16% or more was larger than that of the bullet. In addition, the use of the drug as an antihypertensive agent is increasing because it has little interaction with other drugs and the side effect expression rate is similar to a placebo.

However, olmesartan methoxomile is a hydrophobic material that is difficult to be solubilized at room temperature, and is unstable to light or heat and has a very large poorly soluble property. In addition, olmesartan medoxyl wheat is suppressed by efflux transporters in the gastrointestinal tract such as MDR1 (multidrug resistance 1), BCRP (breast cancer resistance protein) and MRP2 (drug resistance-associated protein 2). Has been reported. To overcome these problems, solubilization technology increases the solubility of the drug and thereby saturates the efflux tramsporter, but since olmesartanmedoxomil is also highly crystalline, There is difficulty.

Patent application No. 10-2003-70067522003 as a domestic patent for olmesartan medoxyl wheat discloses a pharmaceutical composition consisting of an angiotensin II receptor antagonist and one or two or more diuretics. Patent application No. 10- 2007-7026491 discloses a combination of olmesartanmedoxomil, amlodipine besylate combination, and hydrochlorziazide to enhance the treatment of hypertension.

Olmesartanmedoxomil has been reported to have dose-dependent blood pressure lowering effects. Thus, the improvement of solubility and bioavailability of olmesartanmedoxomil would have the effect of improving drug efficacy and reducing drug dose for the same drug. However, there is no formulation research on this.

Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.

The present inventors have tried to develop a self-emulsifying drug delivery system for improving the poor solubility and increasing the bioavailability of olmesartanmethoxomile which is used as a therapeutic agent for hypertension. As a result, when the composition of the active ingredient olmesartanmethoxomile is mixed with an oil, a surfactant, and an auxiliary surfactant, olmesartanmethoxomile is present in a stable microemulsion state in an aqueous solution, and solubility is greatly improved. Rather, the present invention was completed by experimentally confirming that bioavailability is greatly increased by promoting absorption in the gastrointestinal tract.

Accordingly, it is an object of the present invention to provide a composition for the self-emulsifying drug delivery system of olmesartanmedoxomil containing olmesartanmethoxomile, oils, surfactants and cosurfactants.

In addition, another object of the present invention is to provide a method for producing a composition for the self-emulsifying drug delivery system of the olmesartan medoxomil.

Another object of the present invention is to provide an oral capsule formulation comprising the composition for the self-emulsifying drug delivery system of olmesartanmedoxomil.

The objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one aspect of the present invention, the present invention provides a self-emulsifying drug delivery system of olmesartan medoxomil, including olmesartan medoxomil, oils, surfactants and cosurfactants. ) Is provided.

The active ingredient included in the composition of the present invention is olmesartanmedoxomil. Olmesartanmedoxomil is an angiotensin II antagonist, a compound represented by the following general formula (1), is used as an antihypertensive agent, and is a poorly soluble drug insoluble in water.

The content of olmesartan medoxomil in the composition of the present invention is preferably 0.1-10% by weight in the total content of the composition. If the content is less than 0.1% by weight, the content of the excipient is relatively increased, making it difficult to formulate due to the excipient, and the dosage amount is increased. If the content is more than 10% by weight, the dissolution of the active ingredient becomes difficult, and the formation of precipitates during long-term storage is difficult. It is easy and there is a problem that the size of the emulsion produced in contact with water increases exponentially.

The oils used in the compositions of the present invention are those that are well mixed with surfactants and cosurfactants and can be emulsified in water to form stable microemulsions, and pharmaceutically acceptable oils can be used. Examples of the oil that can be used in the present invention include the following.

(1) fatty acid triglycerides, preferably intermediate fatty acid triglycerides, for example fractionated coconut oil (trade name: capriol);

(2) fatty acid mono-, di- or mono / di-glycerides, preferably mono- or di-glycerides of oleic acid;

③ ester compounds of fatty acids and monovalent alkanols, preferably ester compounds of fatty acids having 8 to 20 carbon atoms and monovalent alkanols having 2 to 3 carbon atoms; For example isopropyl myristate, isopropyl palmitate, ethyl linoleate or ethyl oleate;

④ natural vegetable or animal oils such as corn oil, olive oil, soybean oil or fish oil;

⑤ hydrocarbons such as squalene or squalane;

(6) free fatty acids, preferably liquid oleic acid or linoleic acid;

The oil may be used alone or in combination of two or more thereof. Preferably, intermediate fatty acid triglycerides or mixtures thereof can be used. As for content of the said oil, 5-60 weight% is preferable in the composition whole content. If it exceeds 60% by weight, the emulsion particle size increases exponentially and there is a problem that the stability of the emulsion is poor.

According to a preferred embodiment of the present invention, the oil in the present invention is a fatty acid ester of propylene glycol, more preferably Capryol 90 (polyethylene glycol monocaprylate).

Surfactants used in the compositions of the present invention improve the bioabsorbability and bioefficiency of the active ingredient.

The surfactant component of the present invention acts as a dissolving agent to dissolve the poorly soluble active ingredient olmesartanmedoxomil, prevents recrystallization of the drug in the gastrointestinal tract, and stably disperses the drug regardless of acidity and temperature, thereby enabling stable emulsion formation. do. The surfactant of the present invention uses a pharmaceutically acceptable, and since the ionic surfactant is highly irritating and toxic, preferably a nonionic surfactant is used.

According to a preferred embodiment of the present invention, the surfactant used in the composition of the present invention has a HLB (Hydrophilic Lipophilic Balance) value of 7 or more, more preferably HLB value of 10 to 15.

The nonionic surfactants included in the compositions of the present invention are preferably caster oils such as polyoxylated castor oil, substituted caster oils such as Cremophor or hydrogenated Cremophor, twin ( tweens, spans, Labrasol and Brij. More preferably, Tweens and Labrasol are used.

The content of the surfactant in the composition of the present invention is preferably 20-90% by weight in the total composition. If the content of the surfactant is less than 10% by weight, there is a problem that the ability to form an emulsion is low, and the stability of the formed emulsion is lowered, and if it is 90% by weight or more, a desired effect is difficult to be obtained compared to the added amount.

In the present invention, when using Cremophor, Tween, Span or Laborasol as the nonionic surfactant, an efflux pump (efflux) present in the gastrointestinal tract biofilm upon oral administration. Inhibition by the pump can promote the absorption of the drug more.

Cosurfactants in the compositions of the present invention are used to further improve the solubilization capacity and stability of the self-emulsifying drug delivery system. The cosurfactant of the present invention can form a stable microemulsion by stably emulsifying the poorly water-soluble active ingredient olmesartanmedoxomil in water with the surfactant. The auxiliary surfactant of the present invention can be used as long as it has the above characteristics. Examples of the co-surfactant that can be used in the present invention include the following.

1) polyhydric alcohols such as polyethylene glycol, propylene glycol, dimethylisosorbide, diethylene glycol monoethyl ether (transcutol), alpicoat canal oil, propylene glycol monolaurate and tetraglycol;

② esters of polyoxyethylene-sorbitan-fatty acid esters, for example, polyoxyethylene-sorbitan-mono, trilauryl, palmityl, stearyl, oleyl (product name: Polysorbate 80, Tween, ICI));

(3) polyoxyethylene fatty acid esters such as polyoxyethylene stearic acid ester (product name: Myrj, ICI);

④ polyoxyethylene-polyoxypropylene block copolymer (trade name: Poloxamer, Pluronic, Lutrol; BASF);

⑤ mono-, di- or mono / di-glycerides, for example capryl / capric acid mono- or di-glycerides (trade name: Imwitor, Huls);

⑥ sorbitan fatty acid esters such as sorbitan monolauryl, sorbitan monopalmi or sorbitan monostearyl (product name: Span);

⑦ trans-esterification reaction product of natural vegetable oil triglyceride with polyalkylene polyol (trade name: Labrafil).

In the present invention, the HLB value of the cosurfactant is preferably 7 or more, more preferably 12-18.

According to a preferred embodiment of the present invention, a monoester substituted with a polyhydric alcohol of diethylene glycol monoethyl ether [Transcutol] or tetraglycol is used as an auxiliary surfactant in the present invention.

The content of the auxiliary surfactant in the present invention is preferably 10-50% by weight, more preferably 15-50% by weight based on the whole composition of the present invention. If the content of the auxiliary surfactant is less than 10% by weight, there is a problem in dissolving. If the content of the auxiliary surfactant is more than 70% by weight, crystals are precipitated when the nanoemulsion concentrate is diluted in the aqueous phase.

The ratio of the components in the composition of the present invention is a weight ratio, olmesartanmedoxomil: oil: surfactant: cosurfactant = 1: 0.5-50: 0.5-50: 0.5-50, more preferably weight ratio Olmesartan Medoxomil: Oil: Surfactant: Cosurfactant = 1: 5-25: 10-25: 10-25

In addition, a pharmaceutically acceptable carrier may be further added to the composition of the present invention. Pharmaceutically acceptable carriers are conventionally used in the formulation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, poly Vinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

In the composition for the self-emulsifying drug delivery system of the present invention, a daily dosage (commonly used, for adults, is 10 to 80 mg once a day, one to three times a day, usually 1 day for olmesartanmethoxomile) The total amount is usually not more than 200 mg) may be appropriately divided into one to several times.

According to another aspect of the present invention, the present invention comprises olmesartan medoxomil, oil, surfactant and co-surfactant comprising the step of mixing the composition for self-emulsifying drug delivery system of olmesartanmedoxomil It provides a method of manufacturing.

The component olmesartan medoxo mill, oil, surfactant, and auxiliary surfactant constituting the composition of the present invention can be mixed to prepare a self-emulsifying drug delivery system of olmesartan medoxo mill. The components can be prepared in the form of a microemulsion by homogeneous dissolution by mixing and stirring. The microemulsion forms fine emulsion particles having an average diameter of about 300 nm or less when contacted with an aqueous solution.

According to another aspect of the present invention, the present invention provides an oral capsule preparation filled with the composition of the present invention described above.

The composition prepared by the above method may be formulated by filling in a soft capsule according to a conventional pharmaceutical manufacturing process.

As described in detail above, the present invention is to improve the poor solubility of oral bioavailability of olmesartanmedoxomil, a therapeutic agent for hypertension, and the composition for the self-emulsifying drug delivery system containing olmesartanmethoxomile to increase oral bioavailability It relates to a manufacturing method. The composition of the present invention comprises olmesartanmedoxomil as an active ingredient and an oil, a surfactant and an auxiliary surfactant as a solubilizing ingredient. Since the composition of the present invention is in contact with water to form a stable microemulsion state of the active ingredient, the active ingredient can be smoothly absorbed in vivo by oral administration. The composition of the present invention can be included in the capsule formulation and excellent in dispersibility in the water phase can be utilized as a pharmaceutical composition for the development of injections of olmesartan medoxomil.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention. .

Example

Example  One : Self-Emulsified Drug Delivery System  Component oils, surfactants, cosurfactants

Solubility experiments were conducted for each oil, surfactant, cosurfactant, and various pharmaceutically acceptable solvents to find components with high solubility in olmesartan medoxomil.

The solubility of the drug was carried out as follows according to the equilibrium solubility measurement method. First, an excess of olmesartan medoxomil was added to about 5 ml of each solvent, followed by saturation at room temperature for 24 hours. After centrifugation at 13,000 rpm for 10 minutes using a centrifuge, the supernatant was collected and filtered through a 0.45 mm syringe filter (Whatman, Cat. No. 7404004, England), and the filtrate was diluted with methanol and analyzed by HPLC.

HPLC (Shimadzu, Model 10A, Japan) for the HPLC analysis of olmesartanmedoxomil, column was CAPCELLPAK C ₁₈ column (4.6 mm, 150 mm, 5 mm, Shiseido, Japan), acetonitrile: water (pH 3.0) titration with chloroacetic acid) = 20: 80 (v / v) was used, the flow rate 1.0 ㎖ / min, the injection amount 20 ㎖, the analysis wavelength was 260 nm.

The solubility of olmesartanmedoxomil in various oils and surfactants was measured to show a high solubility of 1.29 mg / ml in Capryol 90 in oil. The solubility of 11.81 mg / ml and 4.99 mg / ml in Labrasol, respectively. In addition, the co-surfactant showed solubility of 24.03 mg / ml and 16.7 mg / ml in Tetraglycol and Transcutol, respectively.

Table 1 Solubility Measurement Results

Example 2 Optimization of Proportion of Oil, Surfactant and Auxiliary Surfactant by Creating Phase Equilibria

Based on the solubility measurement results, Capryol 90 as an oil, Tween 20 as a surfactant, Labrasol, Tetraglycol as a surfactant, and Transcutol were used as cosurfactants. After preparing a self-emulsifying drug delivery system, the various phases found by adding water were observed.

The three-component phase equilibrium according to the change of turbidity with increasing amount of water was added to find the ratio of each component forming a microemulsion with a wide contact area with water.

When Tween20 and Tetraglycol were used as surfactants and cosurfactants, the microemulsion area was enlarged when the oil component was 30% or less and the ratio of the surfactant or cosurfactant was 40% or more. This was applied equally when the ratio of surfactant to cosurfactant was 2: 1, 1: 1, 1: 2 (see a, b and c of FIG. 1).

When Labrasol and Transcutol are used as surfactants and cosurfactants, the microemulsion area is enlarged when the oil ratio of 30% or less and the ratio of the surfactant is 50% or more, as described above. It was found that this was applied equally when the ratio of the surfactant and the cosurfactant is 2: 1, 1: 1, 1: 2 (see d, e, f of Figure 1).

Therefore, in each composition, the oil component is 30% or less by weight ratio, and the ratio of the surfactant and the auxiliary surfactant is 2: 1, 1: 1, 1: 2 by weight ratio, and the composition for the self-emulsifying drug delivery system shown in the following table is prepared. Established.

[Table 2] Composition for self-emulsifying drug delivery system

Example 3 Measurement of Particle Size and Emulsion Formation Time of Self-emulsifying Drug Delivery System Composition

After diluting the self-emulsifying drug delivery system composition 100 times in distilled water, the microemulsion was formed and the size of the particles was measured by using dynamic light scattering (DLS). Visual inspection also determined the time required for emulsion formation. The beaker was filled with 500 ml of 37 ° C. distilled water and stirred at a speed of 50 rpm. To this aqueous solution was added dropwise a self-emulsifying drug delivery system composition containing 20 mg / ml of olmesartan medoxomil. The self-emulsifying drug delivery system composition was dispersed in distilled water and again measured the time taken for the entire solution to form a transparent liquid and evaluated it as an emulsion formation time, the experiment was carried out three times.

Capryol 90 as shown in Table 3 : Tween20: Tetraglycol = 10.0: 45.0: 45.0 The composition (type A) showed the smallest particle size and short emulsion formation time of 7.3 ± 1.0 seconds with 11.28 nm particle size. In addition, Capryol 90: Tween 20: Tetraglycol The particle size was 15.63 nm and the emulsion formation time was 19,8 ± 1.0 second in the composition (form D) of 10.0: 60.0: 30.0. In addition, in the composition (G-type) of Capryol 90: Tween 20: Tetraglycol = 10.0: 30.0: 60.0, the particle size was 42.04 nm and the emulsion formation time was 8.8 ± 1.0 second. Based on these results, it was confirmed that A, D, and G self-emulsifying drug delivery system compositions 1, 2, and 3 showed the best characteristics.

Capryol 90: Labrasol: Transcutol = 10.0: 45.0: 45.0 The smallest particle size (210.0 nm) and short emulsion formation time (20.5) for this component ± 2.12 seconds), indicating that it is the best self-emulsifying drug delivery system.

Table 3 Measurement of particle size and emulsion formation time of self-emulsifying drug delivery system composition

Example  4: Rat  Comparison of bioabsorption rate using

4-1. Medication and Blood Collection

The test animals were SD rats (Orient Bio Co., Ltd.), male and 4-5 week old, and the period of purifying was 7 days, and the feed and water were freely ingested (n = 4-5). The test drug (experimental group) was administered the A, D, G, J auto-emulsifying drug delivery system composition formulation of Table 2 containing olmesartan medoxomil, and 1% sodium carboxymethyl cellulose of olmesartan medoxomil (sodium) carboxymethyl cellulose suspension (control) was administered. Doses were administered orally at 1 mg / kg, and blood collection times were taken at intervals of 0, 5, 15, 30 minutes, 1, 2, 4, 8, 12, and 24 hours, and blood samples obtained at each hour were immediately 3,000 rpm. Centrifugation was performed for 10 minutes, and 100 µl of the upper plasma was obtained. Blood collection was done from the femoral vein site.

4-2. Analysis of Olmesartan, an Effective Metabolite in Blood Using LC / MS / MS

Analysis was performed using an MS / MS detector (Positive ion mode, MRM mode). The conditions of the assay were as follows. Olmesartan Medoxomil: m / z 447.3 → 207.2 (Positive) and telmisartan (internal standard): m / z 515.3 → 276.2 (Positive). Desolvation temp. Was 350 ° C., ion spray capillary voltage was 5.5 kV, and Capillary temperature was 500 ° C. Collision energy was 29 eV, and Collision gas used argon. As the nebulizing gas, nitrogen was used, the column was X-terra C ₁₈ , and the data processor was MassLynx 4.1. 5 mM ammonium formate aqueous solution (pH 3.0): acetonitrile = 15: 85 was used as the mobile phase. The flow rate was adjusted to 0.25 mL / min, the injection amount was 10 mu l, and the column temperature was 30 deg.

4-3. Plasma pretreatment

100 μl of a white rat blank plasma was added to a test tube, and 100 μl of olmesartan and 50 μl of telmisartan solution, an internal standard, were added and mixed in a tabletop mixer for 10 seconds. 200 μl of 0.1 M hydrochloric acid was added thereto, followed by acidification, and 5 ml of TBME (tert-butyl methyl ether) as an extraction solvent was added thereto, followed by extraction in a reciprocating shaker for 15 minutes. After centrifugation at 13,000 rpm for 2 minutes, the test tube was placed in a freezer to freeze the aqueous layer. With the water layer frozen, the upper organic layer was taken, transferred to a clean new test tube, and dried completely at 40 ° C. with a nitrogen stream. After drying, 100 μl of the mobile phase was added and redissolved, followed by centrifugation for 5 minutes at 13,000 rpm. The clear top layer was taken, put into a vial and injected into LC-MS / MS.

4-4. Pharmacokinetic Parameter Derivation

The peak blood concentration ( C _max ) and peak blood concentration reaching time ( T _max ) were obtained directly from the blood concentration graph, and the area under the blood curve (AUC) was calculated according to the trapezoidal formula. Relative Bioavailability was calculated from the AUC ratio of olmesartan suspension and the AUC ratio of each formulation. Finally, the results of the drug concentration analysis in the body were verified by Student's t- test (p <0.05). It was.

4-5. Comparison of Bioabsorption Rate

Capryol 90, Tween 20, tetraglycol (Tetraglycol) composition of three self-emulsifying drug delivery system (type A, D, G), capriol 90, Labrasol (Labrasol), transcutol (Transcutol) self-emulsifying drug delivery system composition 1 (J type), a total of four compositions were selected and evaluated the degree of bioavailability improvement compared to drug suspension using a rat animal model. The concentration-time curve of the drug after administration of the plasma suspension and the self-emulsifying drug delivery system composition is shown in FIG. 2, and the pharmacokinetic indicators obtained as a result of blood concentration analysis are shown in Table 4 below.

TABLE 4 Pharmacokinetic Indicators Obtained After Oral Administration of Automated Emulsified Drug Delivery System Composition

When the olmesartanmedoxomil suspension was administered, the blood concentration of the drug gradually increased, reaching T _max 4 hours after administration, and the maximum blood concentration C _max was about 34 ng / ml. Olmesartan methoxomile is a hydrophobic substance having a partition coefficient (log P ) of 4 or more and is considered to be limited in absorption of the drug due to its low solubility because it is a material that is very insoluble in water. On the other hand, the four types of self-emulsifying drug delivery system compositions showed more than three times higher peak blood concentration than the drug suspension, and the time to reach peak blood concentration was reduced from 4 hours to 0.25 minutes. As a result of evaluating the relative bioavailability by comparing the area under the blood concentration curve, it was confirmed that the self-emulsifying drug delivery system increased the body utilization rate of 160-230%. This solution eliminates the dissolution step, which determines the rate of absorption of olmesartan medoxomil through solubilization with oils and surfactants, and also inhibits efflux pumps, causes reversible damage to biological membranes, and comparative groups. It is thought that the absorption and rate of drug absorption were increased through various mechanisms such as decreasing the thickness of the unstirred aqueous layer and increasing the cell gap.

Particularly, the self-emulsifying drug delivery system composition J consisting of Capryol 90, Labrasol and Transcutol has a greater bioavailability improvement effect than the A, D and G compositions. Indicated. In particular, Labrasol used as a surfactant of the self-emulsifying drug delivery system composition J-type not only increases the solubility of poorly soluble drugs but also increases the gastrointestinal absorption of the drug through various actions.

2 and Table 4 As can be seen, the olmesartan medoxomil-containing self-emulsifying drug delivery system composition according to the present invention can significantly increase the absorption of olmesartanmedoxomil in a short time upon in vivo administration can greatly improve the bioavailability.

Having described the specific part of the present invention in detail, it is apparent to those skilled in the art that the specific technology is merely a preferred embodiment, and the scope of the present invention is not limited thereto. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

Figure 1 shows the phase equilibrium tracking the phase change with the addition of water of the oil, surfactant, cosurfactant according to the present invention. The oil was fixed with Capryol 90, and the type and ratio of surfactant and cosurfactant were (a) Tween 20, respectively. Tetraglycol = 2: 1; (b) Tween 20: Tetraglycol = 1: 1; (c) Tween 20 Tetraglycol = 1: 2; (d) Labrasol: Transcutol = 2: 1; (e) Labrasol: Transcutol = 1: 1; (f) Labrasol: Transcutol = 1: 2 was selected. ME stands for microemulsion.

Figure 2 is a pharmacokinetic profile of the self-emulsifying drug delivery system composition A, D, G, J of the present invention.

Claims (11)

A composition for self-emulsifying drug delivery system of olmesartan medoxomil comprising olmesartan medoxomil, oil, surfactant and cosurfactant. The composition of claim 1 wherein the oil is a fatty acid ester of propylene glycol. The composition of claim 2, wherein the fatty acid ester of propylene glycol is Capryol 90 (polyethylene glycol monocaprylate). The composition of claim 1, wherein the surfactant is a nonionic surfactant. The method of claim 4, wherein the nonionic surfactant is selected from the group consisting of castor oil, substituted castor oil, Tweens, spans, and Labrasol. Composition. The composition of claim 1, wherein the co-surfactant is diethylene glycol monoethyl ether [Transcutol] or tetraglycol. The method according to claim 1, wherein the olmesartan medoxomil is 0.1-10% by weight, oil is 5-60% by weight, surfactant is 20-90% by weight, and auxiliary surfactant is 10-50% by weight based on the total composition. A composition, characterized in that. The composition of claim 1, wherein the HLB (Hydrophilic Lipophilic Balance) value of the surfactant or cosurfactant is 7-15. The method of claim 1, wherein the ratio of the components constituting the composition in the composition is olmesartanmedoxomil: oil: surfactant: cosurfactant = 1: 0.5-50: 0.5-50: 0.5-50 by weight ratio Composition. Olmesartan medoxo mill, a method for producing a composition for a self-emulsifying drug delivery system of olmesartan medoxo mill, characterized in that it comprises the step of mixing the oil, surfactant and auxiliary surfactant. An oral capsule formulation, wherein the composition of any one of claims 1 to 9 is filled.

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