KR20200022786A - Controlled-release pharmaceutical composition - Google Patents

Abstract

The present invention relates to a controlled-release pharmaceutical composition which can improve bioavailability of mirabegron and exhibits certain release control properties, so as to enable a user to take the controlled-release pharmaceutical composition once a day. The controlled-release pharmaceutical composition contains: an active component including mirabegron or pharmaceutically acceptable salt thereof; a sustained-release material including hydrophilic polymers; a polyoxyglyceride surfactant; and a pharmaceutically acceptable excipient.

Description

Controlled Release Pharmaceutical Compositions {CONTROLLED-RELEASE PHARMACEUTICAL COMPOSITION}

The present invention relates to a controlled release pharmaceutical composition that can improve the bioavailability of Mirabegron, and exhibits a predetermined release control property, thereby enabling the administration once daily.

Mirabegron is a pharmaceutically active ingredient having the structure of Formula 1, and is known to be mainly useful for treating overactive bladder symptoms.

[Formula 1]

More specifically, the mirabegron can be used as a therapeutic agent for overactive bladder by increasing the bladder storage capacity by relaxing the bladder by acting on the β3 receptor, for example, in addition to the overactive bladder due to enlarged prostate, It has been reported to be useful as a treatment for overactive bladder with urinary incontinence or urinary frequency.

By the way, the Mirabegron is a poorly soluble component insoluble in water, and applied to a general formulation, and conducted clinical trials, it was confirmed that the pharmacokinetic data significantly changed depending on the presence or absence of dietary intake. There is a bar. For example, compared with fasting, the reduction rate of Cmax under predation was 67%, and the reduction rate of AUC was 47%. In addition, it was confirmed that Cmax at the time of fasting was three times higher than that at the time of fasting.

As described above, since the drug of Mirabegron varies greatly depending on whether or not the food is ingested, development of a controlled release pharmaceutical composition has been considered in order to reduce the effect. Representative examples of such controlled release pharmaceutical composition of Mirabegron are representatively described in Korean Patent No. 0507400 and 1524164.

Such known controlled release pharmaceutical compositions typically have a hydrogel-forming polymer such as polyethylene oxide having a high molecular weight of at least 1 million and a correspondingly high viscosity, and a high solubility to infiltrate water inside a formulation such as polyethylene glycol. Hydrophilic additives are shown.

However, such known controlled release pharmaceutical compositions have many disadvantages in that the controlled release properties that allow one-dose daily administration are not properly expressed. Moreover, when using such known compositions, the bioavailability of Mirabegron is very low, about 29% for Mirabegron 25mg tablets, and Mirabegron 50mg tablets are also around 35%. There is a need for improvement in utilization.

Accordingly, there is a continuing need for controlled release pharmaceutical compositions that can improve the bioavailability of Mirabegron and exhibit predetermined release control properties to enable once-daily administration.

Accordingly, the present invention can improve the bioavailability of Mirabegron, and provides a controlled release pharmaceutical composition that can be taken once a day by showing a predetermined release control properties.

Accordingly, the present invention provides an active ingredient including Mirabegron or a pharmaceutically acceptable salt thereof;

Sustained release bases including hydrophilic polymers;

Polyoxy glyceride surfactants; And

Provided is a controlled release pharmaceutical composition comprising a pharmaceutically acceptable excipient.

Since the pharmaceutical composition of the present invention includes a sustained release base such as a specific surfactant and a hydrophilic polymer, etc., it is possible to greatly improve the bioavailability of the Mirabegron, while allowing the daily administration of the Mirabegron-containing formulation. In certain release properties, for example in vitro release tests, it may exhibit controlled release properties such that after 12 hours the drug dissolution rate of the active ingredient from the pharmaceutical composition is at least 80%.

1 is a view showing the results of evaluation of the bioavailability of Example 1 and Comparative Example 1, Experimental Example 2, after the oral administration of the pharmaceutical compositions of Example 1 and Comparative Example 1 to beagle dogs blood concentration measurement of Mirabegron over time The figure which showed the result.

Hereinafter, a controlled release pharmaceutical composition according to a specific embodiment of the present invention will be described in more detail.

According to one embodiment of the invention, active ingredients, including Mirabegron or a pharmaceutically acceptable salt thereof;

Sustained release bases including hydrophilic polymers;

Polyoxy glyceride surfactants; And

There is provided a controlled release pharmaceutical composition comprising a pharmaceutically acceptable excipient.

As a result of continuous experiments by the present inventors, it was confirmed that the use of polyoxyglyceride-based surfactants can greatly improve the bioavailability of the active ingredient Mirabegron.

This is expected because the specific surfactant exhibits the optimized action of the solubilizing agent and / or absorption accelerator of the mirabegron, which is a poorly soluble drug, thereby maximizing the bioavailability of the mirabegron in vivo.

In addition, the composition of the embodiment includes a polyoxyglyceride-based surfactant as described above, and a hydrophilic polymer that can act as a sustained-release base, so that the daily administration of the mirabegron-containing formulation is possible. Release properties, for example in vitro release tests, have shown that after 12 hours it can exhibit controlled release properties such that the drug dissolution rate of the active ingredient from the pharmaceutical composition is at least 80%.

As such, the controlled release pharmaceutical composition of one embodiment may exhibit desirable controlled release properties that allow for a single dose per day while greatly improving the bioavailability of the mirabegron.

On the other hand, in the controlled release pharmaceutical composition of the embodiment, all of the polyoxy glyceride-based surfactant known to be available in the pharmaceutical field can be used as the surfactant without any particular limitation. Such polyoxyglyceride-based surfactants may include a mixture of mono-, di-, or tri-fatty acid esters of glycerol, and mono-, di-esters of polyalkylene glycols such as polyethylene glycol. In addition, linoleyl polyoxylglycerides, oleoyl polyoxylglycerides, lauroyl polyoxylglycerides, and caprylocaproyl polyols, depending on the type of fatty acid included therein. Capylocaproyl polyoxylglycerides, stearoyl polyoxylglycerides (Stearoyl polyoxylglycerides) and the like can be classified into.

Such a polyoxyglyceride-based surfactant interacts with a sustained release base including a hydrophilic polymer, which will be described later, controls the release characteristics of the Mirabegron drug to a desired range, and increases the bioavailability of the Mirabegron. can do.

In a more specific embodiment, the polyoxy glyceride-based surfactant, linoleoyl polyoxyl-6-glyceride (Product Name: Labrafil M2125CS), oleyl polyoxyl-6-glycer One or more selected from the group consisting of a lide (Oleoyl polyoxyl-6-glyceride; product name: Labrafil M1944CS) and lauroyl polyoxyl-6-glyceride (product name: Labrafil M2130CS) can be used. .

On the other hand, the polyoxyglyceride-based surfactant may be included in an amount of 0.002 to 0.2 parts by weight, or 0.01 to 0.2 parts by weight based on 1 part by weight of the active ingredient Mirabegron or a salt thereof, for the entire pharmaceutical composition It may be included in an amount of 0.1 to 5.0% by weight.

If the content of the surfactant is too small, the bioavailability of the mirabegron may not be sufficient, on the contrary, if the content of the surfactant is too large, the composition of one embodiment is formed into a tablet due to the nature of the liquid or semi-solid surfactant. It can be difficult to do.

Meanwhile, the composition of one embodiment may include a hydrophilic polymer as a sustained release base for controlled release, and any hydrophilic polymer capable of acting as a sustained release base may be used without any limitation.

Representative examples of such hydrophilic polymers include one or more selected from the group consisting of polyethylene oxide, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, and carbomer. Various hydrophilic polymers known to be able to function can be used without particular limitation.

Such hydrophilic polymers may have a viscosity average molecular weight of 10,000 to 8,000,000, in order to allow the composition of one embodiment to exhibit appropriate release control properties, at room temperature of 20 to 25 ℃, in an aqueous solution of 1 to 5% by weight It can exhibit a characteristic that the measured viscosity is 3cp to 20,000cp. However, according to the type of each hydrophilic polymer, the molecular weight and viscosity range that can be appropriately used as a sustained release base are well known to those skilled in the art, and thus, further description thereof will be omitted.

The hydrophilic polymers described above may be prepared and used by methods known to those skilled in the art according to the type of each polymer, or may be obtained by using a commercially available hydrophilic polymer as described in the following examples.

On the other hand, in the pharmaceutical composition of the above-described embodiment, the sustained release base including the hydrophilic polymer may be included in an amount of 20 to 80% by weight relative to the weight of the entire pharmaceutical composition. Within this content range, according to the type of each polymer, those skilled in the art can be appropriately selected and used as a content that can properly act as a sustained release base.

On the other hand, the pharmaceutical composition of one embodiment described above further comprises a pharmaceutically acceptable excipient in addition to the active ingredient including a mirabegron or a salt thereof, and a sustained release base including the polyoxyglyceride-based surfactant and a hydrophilic polymer described above. can do. Such pharmaceutically acceptable excipients may typically be diluents (Fillers), glidants, lubricants or film coating agents.

Examples of such excipients are not particularly limited, but as the diluent, lactose, mannitol, starch, cellulose or calcium hydrogen phosphate may be used, and the fluidizing agent may be colloidal silicon dioxide or magnesium metasilica aluminate, or the like. As the lubricant, stearic acid, calcium stearate, magnesium stearate or talc may be used. The film coating base may be a hydroxypropylmethylcellulose or polyvinyl alcohol-based coating base. They are used to improve the physical properties of the manufacturing process and the final product, and are not particularly limited.

The pharmaceutical composition of the embodiment is a combination of the above-described components, that is, the active ingredient, the surfactant, the sustained release base including the hydrophilic polymer and the excipient, and the content of each component can be adjusted so that the total content is 100% by weight.

Although the pharmaceutical composition of one embodiment is obtained with such a simplified component and a manufacturing method employing the same, the optimal drug properties that allow oral administration once a day, for example, in an in vitro release test, after 12 hours have elapsed, It can exhibit drug release properties such that the drug dissolution rate of the active ingredient from the pharmaceutical composition is 80% or more.

In addition, the pharmaceutical composition of the embodiment is as described above that the bioavailability of the Mirabegron can be significantly improved as described above, this can be supported by the experimental example described below.

The preparation method of the pharmaceutical composition of the above embodiment is not particularly limited, and each of the above-mentioned components, for example, an active ingredient, a surfactant, a sustained release base including a hydrophilic polymer, and other excipients are mixed and formulated, and a film coating base It may be prepared according to a conventional method of coating with. The formulation method may be by direct tableting, wet granulation, or dry granulation. Specific manufacturing conditions and methods according to each method are also described in detail in the following examples.

In addition, the formulation form of the pharmaceutical composition of one embodiment is not particularly limited, but may be in the form of a tablet orally taken once daily.

The pharmaceutical composition in the form of a tablet may contain the active ingredient, for example, the Mirabegron or a pharmaceutically acceptable salt thereof in an amount of 25 to 50 mg per tablet.

Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the examples.

Example 1

Mirabegron 10 g, polyethylene oxide (Polyox N-10; viscosity average molecular weight: 100,000; viscosity at 30 ° C. and 5% by weight in aqueous solution: 9.6 g, polyethylene oxide (Polyox 1105; viscosity average molecular weight: 900,000); 29.6 g of viscosity: 8800 to 17600 cP) at 25 ° C. and 5% by weight of an aqueous solution were mixed, placed in a fluidized bed granulator (Freund-Vector, VFC-LAB Micro FLO-COATER), and then fluidized. Linoleoyl polyoxyl- Granules were prepared by spraying a solution of 0.4 g of 6-glyceride (Labrafil M2125 CS) suspended in 7 mL of purified water. Granulated granules were granulated in a 20mesh standard sieve network, 0.4 g of magnesium stearate was added to the mixture, and then lubricated and compressed into tablets (250 mg per tablet) by a tablet press (STP Pharmaceutical Machinery, ZP198).

Example 2

5 g of linoleoyl polyoxyl-6-glyceride (Labrafil M2125 CS) was adsorbed onto 5 g of magnesium metasilicoaluminate (Neusilin US2) and then dispersed to prepare a mixture, and further 50 g of mirabegrin, polyethylene oxide (Polyox N -750; Viscosity average molecular weight: 300,000; Viscosity: 600-1200 Cp) in aqueous solution at 25 ° C and 5% by weight aqueous solution 94 g, polyethylene oxide (Polyox 1105; Viscosity average molecular weight: 900,000; in aqueous solution at 25 ° C and 5% by weight Viscosity: 8800 to 17600 cP) 94g was mixed and mixed. 2 g of magnesium stearate was added to the mixture, and the mixture was lubricated and then granulated by compressing and sizing in a roller compactor (Seoul hightech, RC-60). The granules were compressed into tablets to 250 mg per tablet in a tablet press (STP Pharmaceutical Machinery, ZP198).

Example 3

20 g of linoleoyl polyoxyl-6-glyceride (Labrafil M2125 CS) was adsorbed to 8 g of magnesium metasilicoaluminate (Neusilin US2) and then dispersed to prepare a mixture, and further 200 g of mirabegron and polyethylene oxide (Polyox N -750; Viscosity average molecular weight: 300,000; Viscosity: 600 to 1200 Cp) at 25 ° C. and 5% by weight aqueous solution, 372 g, Polyethylene oxide (Polyox 1105; Viscosity average molecular weight: 900,000; at 25 ° C. and 5% by weight aqueous solution Viscosity: 8800 to 17600 cP) 372g was added and mixed. 8 g of magnesium stearate was added to the mixture, and the mixture was lubricated and then granulated by compressing and sizing in a roller compactor (Seoul hightech, RC-60). 20 g of Cab-o-Sil was added to the granules, mixed, and then compressed into tablets (250 mg per tablet) by a tablet press (STP Pharmaceutical Machinery, ZP198). The tablets were placed in a film coating machine (Sejong Pharmatech, SFC-30FN), and Opadry 03F220071 was poured into purified water to prepare a film coated tablet so as to spray 7.5 mg per tablet.

Example 4

10 g of Mirabegron, polyethylene oxide (Polyox N-60K; viscosity average molecular weight: 2,000,000; viscosity: 2,000 to 4,000 cP in an aqueous solution at 25 ° C. and 2% by weight) 14 g, 25.5 g lactose monohydrate (Pharmatose 200) The solution was placed in a fluidized bed granulator (Freund-Vector, VFC-LAB Micro FLO-COATER), fluidized, and granulated by spraying a solution of 0.1 g of linoleyl polyoxyl-6-glyceride (Labrafil M2125 CS) suspended in 5 mL of purified water. Water was prepared. Granulated granules were granulated in a 20mesh standard sieve network, 0.4 g of magnesium stearate was added to the mixture, and then lubricated and compressed into tablets (250 mg per tablet) by a tablet press (STP Pharmaceutical Machinery, ZP198).

Example 5

Mirabegron 10g, hydroxypropyl methylcellulose (Methocel K100M; viscosity: 100,000cP) 10g, lactose monohydrate (Pharmatose 200) 28.6g mixed and mixed fluid bed granulator (Freund-Vector, VFC-LAB Micro FLO-COATER) After putting in a fluidized solution, 1.0 g of linoleoyl polyoxyl-6-glyceride (Labrafil M2125 CS) suspended in 7 mL of purified water was sprayed to prepare granules. Granulated granules were granulated in a 20mesh standard sieve network, 0.4 g of magnesium stearate was added to the mixture, and then lubricated and compressed into tablets (250 mg per tablet) by a tablet press (STP Pharmaceutical Machinery, ZP198).

Example 6

Mirabegron 10.0 g, hydroxypropyl methylcellulose (Metolose 60SH-50; viscosity at 50 ° C. at 20 ° C. and 2% by weight of aqueous solution: 32.5 g), hydroxypropyl methylcellulose (Pharmacoat 603; 20 ° C. and 2% by weight of Viscosity in aqueous solution: 3cP) 4.5g and 0.8g of colloidal silicon dioxide (Cab-o-Sil) were mixed, fluidized into a fluidized bed granulator (Freund-Vector, VFC-LAB Micro FLO-COATER), and then fluidized. Granules were prepared by spraying a solution of 1.6 g of one polyoxyl-6-glyceride (Labrafil M2125 CS) suspended in 7 mL of purified water. Granulated granules were granulated in a 20mesh standard sieve network, and additionally mixed with 0.6 g of magnesium stearate, and lubricated, and then compressed into a tablet tablet (250 mg per tablet) by a tablet press (STP Pharmaceutical Machinery, ZP198).

Example 7

20 g of oleoyl polyoxyl-6-glyceride (Labrafil M1944 CS) was adsorbed onto 8 g of magnesium metasilicoaluminate (Neusilin US2) and then dispersed to prepare a mixture, and further 200 g of Mirabegron, polyethylene oxide (Polyox N- 750; viscosity average molecular weight: 300,000; viscosity at 25 ° C. and 5% by weight of aqueous solution 372 g, polyethylene oxide (Polyox 1105; viscosity average molecular weight: 900,000; viscosity at 25 ° C. and 5% by weight of aqueous solution : 8800 to 17600 cP) 372g was mixed and mixed. 8 g of magnesium stearate was added to the mixture, and the mixture was lubricated and then granulated by compressing and sizing in a roller compactor (Seoul hightech, RC-60). 20 g of colloidal silicon dioxide (Cab-o-Sil) was added to the granules, mixed, and then compressed into a tablet tablet (250 mg per tablet) by a tablet press (STP Pharmaceutical Machinery, ZP198).

Example 8

20 g of lauroyl polyoxyl-6-glyceride (Labrafil M2130 CS) was adsorbed onto 8 g of magnesium metasilicoaluminate (Neusilin US2) and then dispersed to prepare a mixture, and further 200 g of Mirabegron, polyethylene oxide (Polyox N -750; Viscosity average molecular weight: 300,000; Viscosity: 600 to 1200 Cp) at 25 ° C. and 5% by weight aqueous solution, 372 g, Polyethylene oxide (Polyox 1105; Viscosity average molecular weight: 900,000; at 25 ° C. and 5% by weight aqueous solution Viscosity: 8800 to 17600 cP) 372g was added and mixed. 8 g of magnesium stearate was added to the mixture, and the mixture was lubricated and then granulated by compressing and sizing in a roller compactor (Seoul hightech, RC-60). 20 g of colloidal silicon dioxide (Cab-o-Sil) was added to the granules, mixed, and then compressed into a tablet tablet (250 mg per tablet) by a tablet press (STP Pharmaceutical Machinery, ZP198).

Comparative Example 1

Mirabegron 10 g, polyethylene oxide (Polyox N-10; viscosity average molecular weight: 100,000; viscosity at 30 ° C. and 5% by weight of aqueous solution: 10 g, 10 g, polyethylene oxide (Polyox 1105; viscosity average molecular weight: 900,000; 25 After mixing 29.6 g of viscosity: 8800 to 17600 cP) in an aqueous solution of 5% by weight and putting into a fluidized bed granulator (Freund-Vector, VFC-LAB Micro FLO-COATER), the mixture was fluidized and granulated by spraying 7 mL of purified water. Was prepared. Granulated granules were granulated in a 20mesh standard sieve network, 0.4 g of magnesium stearate was added to the mixture, and then lubricated and compressed into tablets (250 mg per tablet) by a tablet press (STP Pharmaceutical Machinery, ZP198).

Comparative Example 2

Mirabegron 50g, polyethylene oxide (Polyox N-750; viscosity average molecular weight: 300,000; viscosity: 600 to 1200 Cp in an aqueous solution at 25 ° C. and 5% by weight) 97 g, polyethylene oxide (Polyox 1105; viscosity average molecular weight: 900,000; Viscosity: 8800 to 17600 cP) 96g and 5g of magnesium metasilica aluminate (Neusilin US2) were added and mixed in an aqueous solution at 25 ° C. and 5% by weight. 2 g of magnesium stearate was added to the mixture, and the mixture was lubricated and then granulated by compressing and sizing in a roller compactor (Seoul hightech, RC-60). The granules were compressed into tablets to 250 mg per tablet in a tablet press (STP Pharmaceutical Machinery, ZP198).

Comparative Example 3

Mirabegron 10.0 g, hydroxypropyl methylcellulose (Metolose 60SH-50; viscosity at 50 ° C. at 20 ° C. and 2% by weight of aqueous solution: 32.5 g), hydroxypropyl methylcellulose (Pharmacoat 603; 20 ° C. and 2% by weight of Viscosity in aqueous solution: 3cP) 6.1g and 0.8g of colloidal silicon dioxide (Cab-o-Sil) were mixed, fluidized into a fluidized bed granulator (Freund-Vector, VFC-LAB Micro FLO-COATER), and then fluidized. Was sprayed to produce granules. Granulated granules were granulated in a 20mesh standard sieve network, and additionally mixed with 0.6 g of magnesium stearate, and lubricated, and then compressed into a tablet tablet (250 mg per tablet) by a tablet press (STP Pharmaceutical Machinery, ZP198).

Experimental Example 1

The tablets of each of the tablets of Examples 1 to 8 and Comparative Examples 1 to 3 were subjected to a dissolution test under a rotating condition of paddle method and 50 rpm in water solution 900 mL with 37 ° C. and eluent. After starting the dissolution test, 5mL was taken at each sampling point and filtered through a membrane filter, and analyzed by liquid chromatography. The dissolution test results analyzed in this way are summarized in Table 1 below.

Cumulative Dissolution Rate of Mirabegron for Each Hour (%) Minutes 0 180 360 540 720 Example 1 0.0 19.7 50.6 72.6 84.5 Example 2 0.0 22.9 51.8 73.6 84.3 Example 3 0.0 22.1 49.8 69.1 85.4 Example 4 0.0 20.6 49.6 68.7 86.2 Example 5 0.0 30.5 53.4 76.5 88.7 Example 6 0.0 27.6 57.2 79.1 89.6 Example 7 0.0 20.5 49.5 73.4 86.1 Example 8 0.0 23.2 51.6 72.0 85.2 Comparative Example 1 0.0 16.9 40.8 61.8 73.1 Comparative Example 2 0.0 20.3 43.7 62.3 74.1 Comparative Example 3 0.0 23.8 42.6 59.6 73.9

The tablets prepared in Examples 1 to 6 all achieved a target dissolution rate of 80% or more at 720 minutes from the start of dissolution to exhibit a typical sustained release pattern. In contrast, in Comparative Examples 1 to 3, the dissolution rate was less than 80% at 720 minutes, and thus the target dissolution pattern was not shown.

Experimental Example 2 : Mirabegron  Vivo of containing pharmaceutical composition Utilization rate  evaluation

The tablets prepared in Example 1 and Comparative Example 1 were respectively administered to three beagle dogs to confirm bioavailability. After fasting for 16 hours before dosing, the tablets were orally administered, and blood samples were collected at 1, 2, 3, 4, 6, 8, 10, 12, 18, and 24 hour time points to determine the concentration of mirabecron in the blood by LC / MS / MS. It was measured by analyzing. The bioavailability analysis results confirmed by this method are summarized in Table 2 and FIG. 1.

Pharmacokinetic Results of Mirabegron After Oral Dosing in Beagle Dogs division Example 1 Comparative Example 1 AUC _(last) 1195.18 513.25 C _max 151.03 65.05

Referring to Table 2 and Figure 1, Example 1 and Comparative Example 1 showed a significant difference in AUC and Cmax, Example 1 containing a polyoxyglyceride-based surfactant Cmax and AUC compared to Comparative Example 1 All showed 2.3 times higher results. Through this, Example 1 was confirmed to be very superior to Comparative Example 1 in terms of bioavailability.

Claims (7)

Active ingredients, including mirabecron or a pharmaceutically acceptable salt thereof;
Sustained release bases including hydrophilic polymers;
Polyoxy glyceride surfactants; And
Controlled Release Pharmaceutical Compositions Containing Pharmaceutically Acceptable Excipients
According to claim 1, wherein the polyoxyglyceride-based surfactant is linoleoyl polyoxyl-6-glyceride (Linoleoyl polyoxyl-6-glyceride), oleoyl polyoxyl-6-glyceride (Oleoyl polyoxyl-6-glyceride ) And lauroyl polyoxyl-6-glyceride, caprylocaproyl polyoxylglycerides, stearoyl polyoxylglycerides A controlled release pharmaceutical composition comprising at least one kind.
The controlled release pharmaceutical composition of claim 1, wherein the polyoxyglyceride-based surfactant is included in an amount of 0.002 to 0.2 parts by weight based on 1 part by weight of the active ingredient.
The controlled release pharmaceutical composition of claim 1, wherein the sustained-release base comprises at least one selected from the group consisting of polyethylene oxide, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, and carbomer.
The controlled release pharmaceutical composition of claim 1, wherein the sustained release base is included in an amount of 20 to 80 wt% based on the total weight of the pharmaceutical composition.
The controlled release pharmaceutical composition according to claim 1, which has a tablet form which is taken orally once daily.
The controlled release pharmaceutical composition according to claim 1, wherein the Mirabegron or a pharmaceutically acceptable salt thereof is contained in an amount of 25 to 50 mg per tablet.

Images