KR102525298B1 - Carvedilol loaded solid dispersion with increased oral bioavailability and methods for their preparation - Google Patents

Abstract

The present invention relates to a solid dispersion containing carvedilol with increased oral bioavailability and a method for preparing the same, and more particularly, to 100 parts by weight of carvedilol and 12.5 to 50 parts by weight of a surfactant relative to 100 parts by weight of carvedilol It relates to a solid dispersion containing carvedilol containing 10 to 1000 parts by weight of a hydrophilic carrier and 1 to 100 parts by weight of tartaric acid and a method for preparing the same. In addition, the carvedilol-containing solid dispersion according to the present invention may be a solvent evaporation solid dispersion or a surface-attached solid dispersion, and the above two solid dispersions have a significant increase in water solubility and dissolution, and thus oral bioavailability. can improve

Description

Carvedilol loaded solid dispersion with increased oral bioavailability and methods for their preparation}

The present invention relates to a carvedilol-containing dosage form with increased water solubility, dissolution and oral bioavailability using solid dispersion technology and a method for preparing the same, and more specifically, to 100 parts by weight of carvedilol and 100 parts by weight of carvedilol A solid dispersion containing carvedilol containing 12.5 to 50 parts by weight of a surfactant, 10 to 1000 parts by weight of a hydrophilic carrier, and 1 to 100 parts by weight of tartaric acid, with significantly improved water solubility, dissolution rate and oral bioavailability of carvedilol. It's about the body.

Carvedirol is a non-selective β-blocker with α-1 receptor blocking activity, and is a drug used as a treatment for hypertension, congestive heart failure and other left ventricular dysfunction. Its IUPAC name is (±)-1(carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol.

In developing new drugs, it is important to improve the water solubility of drugs. Insufficient water solubility of the drug causes inhibition of absorption and low oral bioavailability. Most of the new drug materials currently being developed are drugs belonging to BCS class II having low water solubility and high membrane permeability. Cavedirol, a model drug of the present invention, is also a drug belonging thereto.

Therefore, in order to improve the water solubility of drugs having such low water solubility, a solid dispersion (Bulletin of the Korean chemical society, 39, 778-783 (2018)), a solid self-emulsifying drug delivery system (Drug delivery, 24(1) ), 1018-1025 (2017)), clathrate compounds (Colloids and Surfaces B: Biointerfaces, 162, 420-426 (2018)), gelatin microspheres (Drug delivery, 17(5), 322-329 (2010)), etc. Several solubilization techniques have been used.

Among them, the solid dispersion technology is a technology that is already widely used in the industrial field and has high potential for practical use. ) and a surface-attached solid dispersion (Colloids and Surfaces B: Biointerfaces, 154, 89-95 (2017)) were used to prepare a formulation with improved water solubility. The solvent evaporation solid dispersion formed in this way converts the drug into an amorphous form and the water-soluble polymer captures it, preventing crystallization and increasing the solubility of the drug in water. A water-soluble polymer is attached to the surface of the drug and converts the hydrophobicity of the drug into hydrophilicity, thereby increasing the drug's water solubility. In general, the solvent evaporation solid dispersion has a greater effect of increasing the water solubility, but the surface-attached solid dispersion has the advantage that the drug is more stable because it does not use a solvent and does not change the crystal form.

1) Patent Publication No. 10-2008-0105114 (nanoparticle-type carvedirol formulation, published on December 3, 2008) 2) Patent Publication No. 10-2005-0061062 (Carvedilol formulation with improved solubility, published on June 22, 2005) 3) Patent Publication No. 10-2014-0037648 (pharmaceutical composition and controlled-release pharmaceutical formulation containing carvedilol and tartaric acid, published on March 27, 2014) 4) Patent Publication No. 10-2001-0031952 (new oral dosage form for carvedirol, published on April 16, 2001)

An object of the present invention is to provide a carvedilol-containing solid dispersion containing tartaric acid with improved water solubility, dissolution and ultimately oral bioavailability, and a method for preparing the same.

However, the problem to be solved by the present invention is not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

According to one embodiment of the present invention, the present invention provides a solid dispersion containing carvedilol, Tween 80, copovidone and tartaric acid as drugs, and a process for preparing the solid dispersion: a) carvedilol, Tween 80, copovidone and preparing a mixed solution containing tartaric acid; b) It provides a manufacturing process comprising the step of drying the manufacturing solution.

The solid dispersion containing carvedilol of the present invention has the effect of significantly increasing the aqueous solubility of carvedilol by dispersing the water-insoluble carvedilol in the hydrophilic polymer copovidone, and further increases the dissolution and oral bioavailability.

1 is a scanning electron micrograph of carvedilol.
2 is a scanning electron micrograph of Comparative Example 5;
3 is a scanning electron micrograph of Comparative Example 8;
4 is a scanning electron micrograph of Example 4;
5 is a scanning electron micrograph of Example 7.
6 is a differential scanning calorimetry graph of carvedilol, Examples 4 and 7, and Comparative Examples 5 and 8.
Figure 7 is a powder X-ray diffraction measurement graph of carvedilol, Examples 4 and 7 and Comparative Examples 5 and 8.
8 is a graph showing drug concentrations in blood after administration of carvedilol, Examples 4 and 7, and carvedilol in an amount corresponding to 40 mg/kg as a drug to SD-based rats.

Hereinafter, the present invention will be described in detail.

According to one aspect of the present invention, Carvedilol comprising 100 parts by weight of Carvedilol, 12.5 to 50 parts by weight of a surfactant, 10 to 1000 parts by weight of a hydrophilic carrier and 1 to 100 parts by weight of tartaric acid based on 100 parts by weight of Carvedilol A containing solid dispersion is provided.

The solid dispersion in the present invention includes all solid dispersions existing in crystalline or amorphous form.

The solid dispersion according to one aspect of the present invention means that the drug, carvedirol, is evenly dispersed in copovidone, a hydrophilic polymer (carrier), and depending on whether the drug is dissolved in a solvent, the crystalline form of the drug is maintained or it is converted into an amorphous form. will be converted The drug is dispersed in copovidone, a hydrophilic polymer, and the properties of the drug are changed to hydrophilic, and the effect of increasing water solubility and dissolution can be obtained. It shows an increasing effect, which leads to an increase in oral bioavailability.

The composition of the carvedilol-containing solid dispersion according to one aspect of the present invention is described as follows:

The surfactant included in the carvedilol-containing solid dispersion of the present invention may be, for example, Tween 80, and the Tween 80 is polyoxyethylene sorbitan monooleate, which corresponds to a solubilizing agent and solid dispersion When the sieve is prepared, it serves to increase the solubility of carvedirol.

The hydrophilic carrier included in the carvedilol-containing solid dispersion of the present invention may be, for example, copovidone, and copovidone refers to a copolymer of vinyl acetate and vinylpyrrolidone. As a result of screening, it showed the best solubilization ability.

As tartaric acid (L-(þ)-2,3-dihydroxybutanedioic acid), tartaric acid corresponds to an acidifying agent and improves the solubility of the formulation by making it acidic by lowering the pH of the formulation.

Meanwhile, according to another aspect of the present invention, the carvedilol-containing solid dispersion may be a solvent evaporation solid dispersion or a surface-attached solid dispersion.

In the composition of the solvent evaporation solid dispersion, it is preferable to contain 12.5 to 50 parts by weight of Tween 80 based on 100 parts by weight of the drug. If the amount of Tween 80 is less than 12.5 parts by weight compared to 100 parts by weight of the drug, sufficient increase in water solubility and dissolution is not shown, and if it exceeds 50 parts by weight, there is no significant increase in water solubility and dissolution, problems may occur during the manufacturing process, and the amount of excipients As this increases, it may cause discomfort during the administration process.

In addition, copovidone may contain 10 to 1000 parts by weight, preferably 50 to 1000 parts by weight, based on 100 parts by weight of the drug. If the amount of copovidone is less than 50 parts by weight relative to the drug weight, sufficient increase in water solubility and dissolution may not be shown, and manufacturing problems may occur. If the amount exceeds 1000 parts by weight, there is no significant increase in water solubility and dissolution, and the amount of excipient As it increases, it may cause discomfort during the administration process.

Meanwhile, tartaric acid may be contained in an amount of 1 to 100 parts by weight, preferably 10 to 100 parts by weight, based on 100 parts by weight of the drug. If the amount of tartaric acid is less than 10 parts by weight of the drug, sufficient increase in water solubility and dissolution may not be shown, and manufacturing problems may occur. If the amount exceeds 100 parts by weight, there is no significant increase in water solubility and dissolution, and the amount of excipients increases. This may cause discomfort during the administration process.

In the composition of the surface-attached solid dispersion, the total amount of Tween 80 and copovidone is preferably 100 to 150 parts by weight based on 100 parts by weight of the drug. If the total amount of Tween 80 and copovidone is less than 100 parts by weight, sufficient water solubility and dissolution increase may not be shown, and if it exceeds 150 parts by weight, problems may occur during manufacturing, and as the amount of excipients increases, inconvenience may occur during administration. can

In addition, the ratio of Tween 80 and copovidone is preferably 3:7. At a ratio of Tween 80 to Cobopidone less than 3:7 (eg, 2:8, etc.), sufficient increase in water solubility and dissolution is not shown, and when the ratio of Tween 80 to Cobopidone exceeds 3:7 (eg, 4:6, etc.), there is no significant increase in water solubility and dissolution.

Meanwhile, the amount of tartaric acid may be 1 to 50 parts by weight, preferably 10 to 50 parts by weight, based on 100 parts by weight of the drug. If the amount of tartaric acid is less than 1 part by weight relative to 100 parts by weight of the drug, sufficient water solubility and dissolution may not be increased, and if the amount exceeds 50 parts by weight, the amount of the excipient increases, which may cause inconvenience during administration.

As a result, the surface-attached solid dispersion containing carvedilol according to one aspect of the present invention contains 100 parts by weight of carvedilol, 30 parts by weight of Tween 80, 10 to 70 parts by weight of copovidone and tartaric acid based on 100 parts by weight of carvedilol. It may contain 1 to 50 parts by weight.

Differential scanning calorimetry (DSC) and powder X-ray diffraction were used to confirm the physicochemical changes of the carvedilol-containing solid dispersion through the examples of the present invention. confirmed that the crystalline form was maintained and confirmed that there was no interaction between the drug and the excipient.

According to one aspect of the present invention, the solvent for preparing the mixed solution may be selected from among acetonitrile, ethanol, methylene chloride, and distilled water, but is not limited thereto.

In the present invention, the method of drying the solvent is not particularly limited, and for example, spray drying using a spray dryer, fluid bed granulator, CF granulator, vacuum dryer, etc., reduced pressure drying, hot air drying, etc. may be used.

The composition according to the present invention may be prepared in a pharmaceutical form including other pharmaceutically acceptable excipients such as diluents, disintegrants, lubricants, etc. in addition to the above components. In addition, the solid dispersion containing carvedilol can be prepared in a pharmaceutical form such as coated tablets, capsules, granules, etc., by a method well known to those skilled in the art.

According to another aspect of the present invention, in the method for preparing a solid dispersion containing carvedilol, (a) preparing a dispersion by mixing carvedirol, a surfactant, a hydrophilic carrier and tartaric acid; And (b) preparing a carvedilol-containing solid dispersion comprising drying the dispersions; It provides a method for producing a solid dispersion containing carvedilol, characterized in that it comprises a.

The surfactant provided according to one aspect of the present invention may be Tween 80, and the hydrophilic carrier may be copovidone.

In addition, the solid dispersion prepared in the manufacturing method of the carvedilol-containing solid dispersion may be a solvent evaporation solid dispersion or a surface-attached solid dispersion.

Hereinafter, embodiments will be described in detail with reference to the accompanying drawings. However, since various changes can be made to the embodiments, the scope of rights of the patent application is not limited or limited by these embodiments. It should be understood that all changes, equivalents or substitutes to the embodiments are included within the scope of rights.

Terms used in the examples are used only for descriptive purposes and should not be construed as limiting. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, terms such as "include" or "have" are intended to designate that there is a feature, number, step, operation, component, part, or combination thereof described in the specification, but one or more other features It should be understood that the presence or addition of numbers, steps, operations, components, parts, or combinations thereof is not precluded.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the art to which the embodiment belongs. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related art, and unless explicitly defined in the present application, they should not be interpreted in an ideal or excessively formal meaning. don't

In addition, in the description with reference to the accompanying drawings, the same reference numerals are given to the same components regardless of reference numerals, and overlapping descriptions thereof will be omitted. In describing the embodiment, if it is determined that a detailed description of a related known technology may unnecessarily obscure the gist of the embodiment, the detailed description will be omitted.

In addition, in describing the components of the embodiment, terms such as first, second, A, B, (a), and (b) may be used. These terms are only used to distinguish the component from other components, and the nature, order, or order of the corresponding component is not limited by the term.

Components included in one embodiment and components including common functions will be described using the same names in other embodiments. Unless stated to the contrary, descriptions described in one embodiment may be applied to other embodiments, and detailed descriptions will be omitted to the extent of overlapping.

Next, a method for preparing a solvent evaporation solid dispersion and a surface-attached solid dispersion according to an embodiment of the present invention and effects thereof are described with reference to the drawings.

- Examples

<Examples 1 to 4> Preparation of solvent evaporation solid dispersion containing carvedilol

(g) Example One 2 3 4 carved roll One One One One twin 80 0.5 0.5 0.5 0.5 copovidone 10 10 10 10 tartaric acid 0.1 0.25 0.5 One

With the composition shown in Table 1, each component was completely dissolved in a 100 ml solution of 95% ethyl alcohol at room temperature and spray-dried to prepare a solvent-evaporated solid dispersion containing carvedilol.

<Examples 5 to 8> Preparation of surface-attached solid dispersions containing carvedilol

With the composition shown in Table 2 below, a hydrophilic carrier, Tween 80, and tartaric acid were completely dissolved in 300 ml of water at room temperature, and then carvedilol was dispersed and spray-dried to prepare a surface-attached solid dispersion containing carvedilol.

(g) Example 5 6 7 8 carved roll One One One One twin 80 0.3 0.3 0.3 0.3 copovidone 0.7 0.7 0.7 0.7 tartaric acid 0.01 0.1 0.25 0.5

<Comparative Examples 1 to 5> Preparation of solvent evaporation solid dispersion containing carvedilol

With the composition shown in Table 3 below, each component was completely dissolved in a 100 ml solution of 95% ethyl alcohol at room temperature and spray-dried to prepare a solvent-evaporated solid dispersion containing carvedilol.

(g) comparative example One 2 3 4 5 carved roll One One One One One twin 80 0.5 0.5 0.5 0.5 0.5 copovidone 0.5 One 2 5 10

<Comparative Example 6-8> Preparation of surface-attached solid dispersion containing carvedilol

With the composition shown in Table 4 below, a hydrophilic carrier, Tween 80, and tartaric acid were completely dissolved in 300 ml of water at room temperature, and then carvedilol was dispersed and then spray-dried to prepare a surface-attached solid dispersion containing carvedilol.

(g) comparative example 6 7 8 carved roll One One One twin 80 0 0.2 0.3 copovidone One 0.8 0.7

<Comparative Example 9> Preparation of solvent evaporation solid dispersion containing carvedilol and tartaric acid

With the composition shown in Table 5 below, each component was completely dissolved in a 100 ml solution of 95% ethyl alcohol at room temperature and spray-dried to prepare a solid dispersion containing carvedilol and tartaric acid by evaporation of solvent.

(g) comparative example 9 carved roll One twin 80 0.5 copovidone 10 tartaric acid 2

<Experimental Example 1> Evaluation of aqueous solubility and dissolution of carvedilol and carvedilol-containing formulations in aqueous solution

Examples 1 to 8 and Comparative Examples 1 to 9 prepared above were prepared and an excess amount (10 mg equivalent as a drug) was added to 1 mL of purified water, followed by stirring at 25 ° C. and 100 rpm in a stirring thermostat for 72 hours. Carvedirol was quantified using the following high-performance liquid chromatography (HPLC) system.

Column: Hypersil ODS-2 ^® C18 (4.6 Х 150 mm, 5 μm)

Flow rate: 1.0 mL/min

Injection volume: 10 μL

Detection wavelength: 242 nm

Mobile phase: Mobile phase A- 0.2% phosphoric acid aqueous solution, mobile phase B- methyl alcohol (50:50 v/v)

In addition, 25 mg of the corresponding amounts of Examples 1 to 8 and Comparative Examples 1 to 9 prepared above were taken as drugs and tested according to the following elution conditions, and high performance liquid chromatography (HPLC) of the aqueous solubility test method with the eluate Carvedilol was quantified by the system.

○ Elution conditions

Eluent: 900 ml of water

Elution temperature: 37 ℃

Elution method: 2nd method (paddle method)

Paddle rotation speed: 50 rpm

Water solubility (μg/mL) Dissolution rate at 30 minutes (%) Example 1 7207.3 ± 257.9 87.2 ± 2.5 Example 2 35000.0 ± 200.0 95.6 ± 1.4 Example 3 40000.0 ± 500.0 95.7±1.0 Example 4 53188.5 ± 5357.4 96.1 ± 1.4 Example 5 867.2 ± 17.1 18.0 ± 3.6 Example 6 1706.4 ± 19.1 32.7 ± 1.9 Example 7 2199.8 ± 126.0 85.6 ± 1.3 Example 8 2899.2 ± 11.2 92.9±1.8 Comparative Example 1 72.5 ± 12.7 15.9 ± 0.8 Comparative Example 2 219.9 ± 6.1 18.9 ± 0.5 Comparative Example 3 596.7 ± 19.0 28.7 ± 0.4 Comparative Example 4 652.2 ± 47.4 33.6 ± 9.1 Comparative Example 5 677.7 ± 40.0 24.8±5.6 Comparative Example 6 57.3±1.8 10.1 ± 2.4 Comparative Example 7 82.1 ± 1.8 13.0 ± 1.2 Comparative Example 8 127.5 ± 9.9 23.4 ± 1.9 Comparative Example 9 2945.1 ± 30.6 95.1 ± 4.9 carvedilol raw material 9.6 ± 0.7 13.8 ± 0.4

In [Table 6], the solvent evaporation solid dispersions of Examples 1 to 4 and the surface-attached solid dispersions of Examples 5-8 were compared with the solvent-evaporated solid dispersions of Comparative Examples 1-5 and the surface-attached solid dispersions of Comparative Examples 6-8. The solid dispersion was evaluated for water solubility and dissolution of the carvedilol raw material.

In the formulations of Examples 1 to 8 and Comparative Examples 1 to 5, 8 and 9, both water solubility and dissolution were significantly increased compared to the raw material for carvedilol. In Comparative Examples 1 to 5, when the amounts of the drug and Tween 80 were fixed in the solvent evaporation solid dispersion and the water solubility and dissolution according to the amount of copovidone were observed, the water solubility increased significantly up to 500 parts by weight of copovidone compared to 100 parts by weight of the drug. appeared, but in excess of 500 parts by weight, significant water solubility and dissolution rate increase did not appear. For this reason, in Examples 1 to 4, when the amount of drug, Tween 80, and copovidone were fixed in the solvent evaporation solid dispersion and the water solubility and dissolution according to the amount of tartaric acid were observed, the aqueous solubility of up to 100 parts by weight of tartaric acid relative to 100 parts by weight of drug Although a significant increase was shown, in excess of 100 parts by weight (Comparative Example 9), no significant increase in water solubility and dissolution rate was observed. In the surface-attached solid dispersion, Comparative Examples 6 to 8 fixed the total amount of the drug, Tween 80, and copovidone, and then increased the ratio of Tween 80 / copovidone, and when water solubility and dissolution were observed, the ratio of Tween 80 / copovidone When this increased to 0.3/0.7, there was a significant increase in water solubility. Through this, when the ratio of the drug and Tween 80 / copovidone was fixed and the water solubility and dissolution according to the amount of tartaric acid were observed (Examples 5 to 8), there was a significant increase in water solubility up to 50 parts by weight of tartaric acid relative to 100 parts by weight of the drug. However, in excess of 50 parts by weight, it was difficult to prepare a surface-attached solid dispersion, and significant water solubility and dissolution rate increase did not appear.

<Experimental Example 2> Physical and chemical property test of carvedilol-containing solid dispersion

The shapes of the drug and the two solid dispersions were compared by taking scanning electron microscope (SEM) pictures of the carvedilol raw material, Examples 4 and 7, and Comparative Examples 5 and 8. As a result of the SEM photograph of FIG. 1, the drug had an irregular shape, but in FIG. 4 (Example 4), it was confirmed that the shape was converted to a circular shape, and in FIG. 5 (Example 7), the carrier was attached to the surface of the irregular drug due to tartaric acid. shape was observed. In Figure 2 (Comparative Example 5), it was confirmed that the shape of the drug was converted to a circular shape, and in Figure 3 (Comparative Example 8), the shape of the delivery agent attached to the irregular shape of the drug was observed.

The differential scanning calorimetry (DSC) of the carvedilol raw material, Examples 4 and 7, and Comparative Examples 5 and 8 was measured to confirm their crystalline form and interaction. Differential scanning calorimetry was carried out in the temperature range of 0 ~ 200 ℃, and the temperature was raised at 10 ℃ per minute. As a result of the DSC of FIG. 6, the carvedilol raw material forms a melting point at around 120 ° C., and the melting point peak disappears in Examples 4 and 7 and Comparative Example 5, confirming that the drug is converted to an amorphous form. In Comparative Example 8, it can be confirmed that the drug maintained its crystalline form, as the melting point peak appeared around about 120 °C.

Powder X-ray diffraction (PXRD) of the raw material for carvedilol, Examples 4 and 7, and Comparative Examples 5 and 8 was measured to confirm their crystalline forms. As a result of the photograph of FIG. 7, it was confirmed that the crystalline form of the drug was converted to an amorphous form, as the specific peaks of the drug on PXRD in Examples 4 and 7 and Comparative Example 5 disappeared. On the other hand, in Comparative Example 8, it was confirmed that the crystalline form was maintained by showing a specific peak of the drug.

<Experimental Example 3> In vivo kinetics of carvedilol-containing solid dispersion (Pharmacokinetics)

To evaluate the oral bioavailability, the raw materials of Examples 4 and 7, carvedilol, were orally administered to SD rats at 40 mg/kg, and blood was collected from the femoral artery using a heparinized disposable syringe. The collected blood was separated from plasma, concentrated by liquid-liquid extraction, and the plasma pretreated using sildenafil citrate as an internal standard was analyzed under the following high-performance liquid chromatography conditions.

Column: Hypersil ODS-2 (4.6 Х 250 mm, 5 μm)

Flow rate: 0.8 mL/min

Injection volume: 50 μL

Detection wavelength: 242 nm

Mobile Phase: Mobile Phase A- 30 mM potassium phosphate aqueous solution, Mobile Phase B- Acetonitrile (60:40 v/v), pH 2.5

The following [Table 7] shows the pharmacokinetic parameters, and FIG. 8 shows the drug concentration in the body according to time.

Pharmacokinetic parameters carvedilol raw material Example 4 Example 7 ¹⁾ T _max (hr) 2.00 ± 0.00 2.00 ± 0.00 2.00 ± 0.00 ²⁾ _Cmax (μg/ml) 0.75 ± 0.12 1.97 ± 0.52 1.39 ± 0.35 ³⁾ AUC (hr×μg/ml) 9.06 ± 2.80 21.21 ± 3.89 15.26 ± 2.56 ⁴⁾ K _el (hr ^-1 ) 0.02 ± 0.02 0.029 ± 0.0043 0.030 ± 0.0027 ⁵ )t _1/2 (hr) 29.94 ± 29.44 23.79 ± 2.70 23.27 ± 2.308

Each figure means "mean ± S.D." (n=6)

1) indicates the time to reach the maximum blood concentration.

2) shows the maximum blood concentration.

3) shows the area under the blood concentration-time curve.

4) represents the elimination rate constant of the drug.

5) represents the half-life of the drug.

Compositions according to the present invention, Examples 4 and 7, compared to the raw material of carvedirol, showed a significant increase in the area under the blood concentration-time curve, which is an indicator of oral bioavailability. A significant increase was also observed in the highest plasma concentration. Therefore, it was confirmed that the composition of the present invention exhibited excellent oral bioavailability.

As described above, although the embodiments have been described with limited drawings, those skilled in the art can apply various technical modifications and variations based on the above. For example, the described techniques may be performed in an order different from the method described, and/or the components of the described system, structure, device, circuit, etc. may be combined or combined in a different form than the method described, or other components may be used. Or even if it is replaced or substituted by equivalents, appropriate results can be achieved.

Therefore, other implementations, other embodiments, and equivalents of the claims are within the scope of the following claims.

Claims (16)

A solid dispersion containing 100 parts by weight of Carvedilol, 12.5 to 50 parts by weight of Tween 80, 800 to 1000 parts by weight of Copovidone, and 10 to 100 parts by weight of tartaric acid based on 100 parts by weight of Carvedilol.
According to claim 1,
The carvedilol-containing solid dispersion is characterized in that the solvent evaporation solid dispersion, carvedilol-containing solid dispersion.
delete delete According to claim 2,
Characterized in that it comprises 50 parts by weight of Tween 80 compared to 100 parts by weight of the carvedilol, carvedilol-containing solid dispersion.
delete delete delete delete According to claim 1,
Characterized in that it further comprises at least one additive selected from the group consisting of pharmaceutically acceptable excipients, diluents, disintegrants, coloring agents and lubricants that do not have a carrier function of the solid dispersion, carvedilol-containing solid dispersion.
In the method for preparing a carvedilol-containing solid dispersion,
(a) preparing a dispersion by mixing carvedilol, Tween 80, copovidone and tartaric acid; and
(b) preparing a carvedilol-containing solid dispersion comprising drying the dispersions;
including,
The solid dispersion comprises 100 parts by weight of Carvedilol, 12.5 to 50 parts by weight of Tween 80, 800 to 1000 parts by weight of Copovidone and 10 to 100 parts by weight of tartaric acid relative to 100 parts by weight of Carvedilol , Manufacturing method of carvedilol-containing solid dispersion.
delete According to claim 11,
The carvedilol-containing solid dispersion is a method for producing a solid dispersion containing carvedilol, characterized in that the solvent evaporation solid dispersion.
delete According to claim 13,
Step (a) comprises completely dissolving carvedilol, Tween 80, copovidone and tartaric acid, respectively, in at least one solvent selected from the group consisting of acetonitrile, ethanol, methylene chloride and distilled water;
Step (b) is a method for producing a solid dispersion containing carvedilol, comprising spray-drying the solution dissolved in step (a).
delete

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