KR20190086138A - Pharmaceutical composition comprising Tamsulosin and Tadalafil - Google Patents

Abstract

The present invention relates to a pharmaceutical composition comprising a drug coating layer, which, in order to control the release of active components of tamsulosin and tadalafil, comprises: a core layer comprising tamsulosin; an enteric coating layer comprising an enteric base coating the core layer; and tadalafil coating the enteric coating layer. The complex formulation exhibit excellent solubility, dissolution rate, and bioavailability.

Description

Pharmaceutical compositions comprising Tamsulosin and Tadalafil (Pharmaceutical composition comprising Tamsulosin and Tadalafil)

The present invention relates to a pharmaceutical composition comprising Tamsulosin or a pharmaceutically acceptable salt thereof and Tadalafil or a pharmaceutically acceptable salt thereof. Specifically, in order to regulate the release of the active ingredient of tamsulosin and tadalafil, a drug comprising a core layer comprising tamsulosin, an enteric coating layer comprising a penetrating base for coating the core layer, and a tadalafil coating the enteric coating layer And a coating layer.

It is known that urinary problems due to benign prostate hyperplasia (BPH) are common in men, and more than 80% of patients with erectile dysfunction experience prostatome enlargement. Erectile dysfunction occurs because of the lack of arterial blood flow to the penis, which can lead to deformation of the prostate gland. In many cases, erectile dysfunction treatment and prostatic hypertrophy treatment are also prescribed at the actual prescription site.

Prostate hyperplasia is a very common symptom in the male elderly. The cause of the disease is closely related to aging and male hormones, and the prevalence increases with age. In 40 ~ 70% of patients aged 60 years or older, Lower Urinary Tract Symptoms: LUTS). Therefore, many studies have been conducted to treat urinary incontinence and prostate hypertrophy as a combination therapy.

Prostate hyperplasia is caused by the enlarged prostate, which closes the outlet of the bladder. The α1 receptor is increased in the prostate to induce excessive contraction of the prostate smooth muscle to discharge the urine. The bladder muscle is thickened, It is a symptom in which the mucous membrane between the muscle fibers is elevated. It can not discharge urine well during urination, frequent urination, decreased strength and thickness of urinary trunk, and delayed onset of urination.

Thus, for example, α1 receptor antagonists such as tamoxifen, prazosin, alpuzosine, naphthopyridyl, and urafidil are used as agents that relax the urethral smooth muscle and weaken the urethral resistance, . However, attention should be paid to the treatment because of side effects such as orthostatic hypotension.

As a prostate smooth muscle-selective alpha 1 blocker, testosterone is useful for dysuria due to benign prostatic hyperplasia. Oral doses are 0.2 to 0.8 mg per day.

It is known that tamsulosin has high selectivity for prostate smooth muscle and low action on blood vessels unlike other α1 blockers such as Doxazosin and Terazosin.

Despite the high selectivity for prostate smooth muscle, however, elevated initial drug concentrations in the blood lead to adverse effects such as orthostatic hypotension, because in vivo absorption of the testosterone is also very rapid.

Although the preferred dosage form of tamsulosin is known to be a delayed and sustained release sustained-release preparation, formulation development is limited in the development of a combination drug with tadalafil, which should be released in the early stage. In addition, in the case of a combined preparation of tamsulosin and tadalafil, the system is totally destroyed due to the occurrence of a specific factor or a deficiency of some components, and the drug release occurs at a time, which may cause serious side effects such as orthostatic hypotension, Special attention should be paid to the development of formulations of complex formulations.

Accordingly, there is a need for a composition and a composition for controlled release which can release tadalafil in a short period of time, while controlling the side effect of rapid drug release and sustaining the effect of the drug, Research is still needed.

The present inventors have made efforts to develop a combined preparation exhibiting excellent dissolution rate and bioavailability as a preparation containing both tamsulosin and tadalafil simultaneously to treat erectile dysfunction and hypertrophy of the prostate.

As a result, a pH-dependent drug release was induced by coating the core layer containing the tamsulosin with a long-acting base and tabletting and adding a water-soluble polymer to the long-acting base. In addition, excellent dissolution and dissolution rate were exhibited by dispersing and coating tadalafil drug outside the enteric coating layer.

In addition, the present invention has been accomplished by confirming that the preparation of the tadalafil preparation is excellent in dissolution compared with the conventional pulverization raw materials.

The present invention relates to a combined preparation containing tamsulosin and tadalafil, and more particularly, to provide a combination preparation exhibiting excellent dissolution rate and bioavailability for the purpose of simultaneously treating erectile dysfunction and enlargement of the prostate gland.

The present invention also provides a combination preparation comprising a core layer comprising tamsulosin or a pharmaceutically acceptable salt thereof, an enteric coating layer and a drug coating layer comprising tardifilm or a pharmaceutically acceptable salt thereof.

In particular, the present invention provides a combined preparation characterized in that the dissolution rate of the test drug is below 20% up to 12 hours at pH 4.0 or lower.

The present invention relates to a pharmaceutical composition containing simultaneously tamsulosin and tadalafil.

The pharmaceutical composition of the present invention has the purpose of treating erectile dysfunction and enlargement of the prostate simultaneously, and exhibits excellent dissolution rate and bioavailability.

For the purpose of inducing pH-dependent drug release, the present invention is characterized in that a core layer comprising tamsulosin is coated with a long-acting base and purified, and a water-soluble polymer is added to the long-acting base to form an enteric coating layer, .

In addition, the present invention provides a formulation in which tomosin is delayed release, in order to prevent side effects (such as orthostatic hypotension) through temporary premature release of tomosin.

Further, the present invention shows an excellent dissolution rate as compared with general pulverization raw materials by preparing a tadalafil preparation as a suspension.

The present invention relates to a pharmaceutical composition for controlled release comprising a core layer comprising tamsulosin or a pharmaceutically acceptable salt thereof, an enteric coating layer comprising a penetrating base, and a drug coating layer comprising tadalafil or a pharmaceutically acceptable salt thereof, Composition.

The present invention relates to a combination preparation containing both tamsulosin and tadalafil, which can simultaneously treat erectile dysfunction and hyperplasia of the prostate, and exhibits excellent solubility, dissolution rate and bioavailability.

In particular, the present invention allows for the delayed release of tamsulosin, thereby reducing side effects due to temporary release of tamsulosin.

FIG. 1 shows a test result of a test strain according to the presence or absence of an enteric coating layer at a pH of 1.2.
FIG. 2 shows a test result of a testosterone elution test according to the presence or absence of an enteric coating layer at pH 4.0.
Fig. 3 shows the results of the test for dissolution of testosterone with or without an enteric coating layer under the condition of pH 6.8.
Fig. 4 shows the result of the test for dissolution of testosterone in the presence of an enteric coating layer under water conditions.
FIG. 5 shows the results of a tadalafil elution test under the condition of 0.5% sodium lauryl sulfate (SLS) pH 1.2.
FIG. 6 shows the results of the test for dissolution test according to the weight% of the enteric coating layer at pH 4.0.
FIG. 7 shows a test result of a test strain according to the weight% of the enteric coating layer at pH 6.8.
FIG. 8 shows a test result of a test strain according to the composition of the core layer at pH 4.0.

The present invention provides a pharmaceutical composition comprising a core layer comprising tamsulosin or a pharmaceutically acceptable salt thereof;

An enteric coating layer comprising a nutrient base coating the outside of the core layer; And

A pharmaceutical coating composition comprising a drug coating layer coated on the outside of the enteric coating layer and comprising tadalafil or a pharmaceutically acceptable salt thereof.

The core layer may further comprise one or more matrix-type sustained release agents. The matrix-type sustained release agent may be selected from the group consisting of methacrylic acid copolymer, methacrylic acid-ethyl acrylate copolymer, methacrylic acid-methyl methacrylate copolymer, hydroxypropylmethylcellulose phthalate and hydroxypropylmethylcellulose acetate succinate But the present invention is not limited thereto.

The matrix type sustained release agent may preferably be a methacrylic acid copolymer, and more preferably, it may be Eudragit.

The core layer preferably contains 10 to 20% by weight, and more preferably 12 to 18% by weight, of the eudragit based on the weight of the core layer.

The nutritive base may be selected from the group consisting of eudragit, zein, shellac, and hydroxypropylmethylcellulose phthalate, but is not limited thereto. In addition, the enteric base agent may preferably be edible.

By adding a water-soluble polymer to the enteric base, the drug can be induced to release from the top to the intestine in a pH-dependent manner.

The water-soluble polymer is selected from the group consisting of methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethylcellulose, hydroxyethylethylcellulose, water-soluble salts of carboxymethylcellulose, and water-soluble salts of carboxymethylhydroxyethylcellulose Polyvinylpyrrolidone (PVP), copolymers of N-vinylpyrrolidone and vinyl acetate or vinyl propionate, polyvinylcaprolactam-polyvinyl acetate-polyvinylpyrrolidone copolymers, Block copolymers of ethylene oxide and propylene oxide also known as polyethylene glycol graft copolymers, polyoxyethylene polyoxypropylene block copolymers or polyoxyethylene polypropylene glycols, such as poloxamer, lauroylpolyoxyglyceride Cellulose esters and There are rules Los ethers, hydroxyalkyl cellulose, polyalkylene oxide polymer, polyvinyl acetate polymer, a partially hydrolyzed polyvinyl acetate, polyvinyl alcohol, and the like.

In addition, the enteric coating layer may further include, but is not limited to, hypromellose and triethyl citrate. By using hypromellose in addition to the enteric coating layer, it is possible to dissolve the water-soluble polymer, hypromellose, during the process of moving the tablet from the upper part to the upper part, thereby continuously releasing the drug. When triethyl citrate is added to a coating agent, it acts as a plasticizer in the coating liquid to impart flexibility and elasticity to the coating layer.

The enteric coating layer is preferably contained in an amount of 3 wt% to 10 wt% based on the weight of the core layer.

The drug coating layer may further comprise hypromellose. In addition, the drug coating layer may be prepared from a suspension in which tadalafil and hypromellose are dispersed. And a suspension in which tadalafil is dispersed in hypromellose, exhibits an excellent dissolution rate as compared with general pulverization raw materials.

The suspension of tadalafil and hydromellose in a weight ratio of 1: 0.1 to 1: 2 is preferable, and a weight ratio of 1: 0.5 to 1: 1 is further preferred.

The present invention relates to an agent for regulating the release of the pharmaceutical composition. The preparation may be a tablet for oral administration.

In addition, the release-controlling agent of the present invention preferably exhibits a tomoskocin dissolution rate of 20% or less at pH 4.0 or lower for 12 hours.

The present invention relates to a pharmaceutical composition comprising: (i) a core layer comprising tamsulosin or a pharmaceutically acceptable salt thereof and an Eudragit; (ii) an enteric coating layer comprising eudragit, triethyl citrate, and hypromellose; And (iii) a drug coating layer comprising tadalafil or a pharmaceutically acceptable salt thereof.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are for further illustrating the present invention, and the scope of the present invention is not limited by these examples.

[Example 1]

Combination of tamsulosin and tadalafil containing enteric coating layer

Tablets (Example 1) comprising a core layer comprising tamsulosin, an enteric coating layer and a drug coating layer comprising tadalafil were prepared with the compositions of Table 1 below.

Constituent Example 1 Weight (mg) ratio(%) Primary granule Tamsulosin hydrochloride 0.2 0.15 Eudragit 18.0 13.64 Mannitol 70.8 53.64 Microcrystalline cellulose 35.0 26.52 After mixing Mannitol 6.0 4.55 Sodium stearyl fumarate 2.0 1.52 Core layer (Raw) Gross weight 132.0 100.0 Enteric coating layer Eudragit 4.0 66.67 Triethyl citrate 0.5 8.33 Hypromellose 1.5 25.00 Gut Coating Layer Gross Weight 6.0 100.0 Drug coating layer Tadalafil 5.0 38.46 Hypromellose 4.0 30.77 Polyethylene glycol 4.0 30.77 Drug coating layer gross weight 13.0 100.0 Gross weight 151.0 -

Step 1. Preparation of Tomrose granules

0.2 mg of testosterone hydrochloride and 18.0 mg of Eudragit were dissolved in ethanol and dissolved by stirring to prepare a binding solution. Thereafter, 70.8 mg of mannitol and 35.0 mg of microcrystalline cellulose were mixed in a high-speed mixer, followed by incorporation of a tamsulosin binding solution to prepare tomosin granules. After coalescence, it was granulated by passing through Co-mil and dried at 50 ° C. The dried material was passed through a Co-mil to formulate it.

Step 2. Final mixing and tableting with new core tablet

The granules of step 1 were put into a mixer, 6.0 mg of mannitol and 2.0 mg of stearyl sodium fumarate were added and mixed to prepare a final mixture, which was then tableted using a tablet machine.

Step 3. Manufacture of enteric coatings

4.0 mg of Eudragit, 0.5 mg of triethyl citrate, and 1.5 mg of hydroxypropylmethylcellulose were added to purified water, and the mixture was stirred and suspended to prepare an enteric coating layer solution. Thereafter, the tablets prepared in step 2 were put into a coater and coated to prepare enteric coated tablets.

Step 4. Manufacture of drug coating definition

5.0 mg of tadalafil, 4.0 mg of hypromellose, and 4.0 mg of polyethylene glycol were placed in purified water and suspended to prepare a tadalafil suspension solution. Thereafter, the enteric coating tablets obtained in step 3 were put into a coater and the coating was carried out to obtain coating tablets.

[Comparative Example 1]

Combination of tamsulosin and tadalafil with no enteric coated layer

Tablets (Comparative Example 1) comprising a core layer comprising tamsulosin and a drug coating layer containing tadalafil in the composition shown in Table 2 below and containing no enteric coating layer were prepared.

Constituent Comparative Example 1 Weight (mg) ratio(%) Primary granule Tamsulosin hydrochloride 0.2 0.15 Eudragit 18.0 13.64 Mannitol 70.8 53.64 Microcrystalline cellulose 35.0 26.52 After mixing Mannitol 6.0 4.55 Sodium stearyl fumarate 2.0 1.52 Core layer (Raw) Gross weight 132.0 100.0 Drug coating layer Tadalafil 5.0 38.46 Hypromellose 4.0 30.77 Polyethylene glycol 4.0 30.77 Drug coating layer gross weight 13.0 100.0 Gross weight (mg) 145.0 -

In Comparative Example 1, tablets were prepared by proceeding in the same manner as in Example 1 except for the step 3 except that a enteric coating was excluded.

[Test Example 1]

Tamsuro Shin dissolution test according to presence or absence of enteric coating layer

The tablets prepared in Example 1 and Comparative Example 1 and 0.2 mg of commercially available Day-Date Dijung (Tomlinsin hydrochloride, manufactured by Astellas Pharma Co., Ltd.) were subjected to a dissolution test under the following conditions.

[Dissolution Test Method]

- Dissolution method: Korean Pharmacopoeia dissolution test method 2 (paddle method)

- Test solution: pH 1.2, 4.0, 6.8, water

- Leaching temperature: 37 ± 0.5 ℃

- Rotation speed: 50 rpm

- Test time: 30 minutes, 60 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes, 720 minutes (7 points)

[Analytical HPLC (liquid chromatographic method) conditions]

- Detector: Absorber spectrophotometer (measuring wavelength: 225 nm)

- Column: Kromasil C8 (4.6 x 100 mm, 3.5 탆) or equivalent column

- mobile phase: a mixture of pH 2.0 buffer ^* and acetonitrile (6: 4)

* pH 2.0 buffer: 8.7 mL of perchloric acid and 3.0 g of sodium hydroxide are precisely weighed, placed in a 2-L capacity flask, dissolved in water and adjusted to pH 2.0 with sodium hydroxide solution

- Injection volume: 500 μl

- Flow rate: 1.0 mL / min

The dissolution test results are shown in Figs. 1 to 4. Fig.

As shown in FIG. 1, the tablets of Comparative Example 1 without the enteric layer at pH 1.2 immediately released the drug, whereas the tablet of Comparative Example and Example 1 showed almost no drug release until 120 minutes.

As shown in FIG. 2, at a pH of 4.0, the control agent and the tablet of Comparative Example 1 released more than 50% of the drug up to 720 minutes, while the tablet of Example 1 showed about 10% of drug release.

As shown in Figures 3 and 4, the tablets of the control, comparative example 1 and example 1 at pH 6.8 and water showed similar release results up to 720 minutes.

As a result, it was confirmed that Example 1 having an enteric coating layer had an excellent release control effect in all the pH ranges tested, as compared with Comparative Example 1 and the comparative drug.

[Test Example 2]

Tadalafil dissolution test

Example 1 The elution test was carried out under the following conditions with the tablets.

[Dissolution Test Method]

- Dissolution method: Korean Pharmacopoeia dissolution assay method 1 (rotation specimen method)

- Test solution: 0.5% SLS pH 1.2

- Leaching temperature: 37 ± 0.5 ℃

- Rotation speed: 50 rpm

- Test time: 5 minutes, 10 minutes, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes (8 points)

[Analytical HPLC (liquid chromatographic method) conditions]

- Detector: Absorber spectrophotometer (measuring wavelength: 225 nm)

- Column: Kromasil C8 (4.6 x 100 mm, 3.5 탆) or equivalent column

- mobile phase: a mixture of pH 2.0 buffer ^* and acetonitrile (6: 4)

* pH 2.0 buffer: 8.7 mL of perchloric acid and 3.0 g of sodium hydroxide are precisely weighed, placed in a 2-L capacity flask, dissolved in water and adjusted to pH 2.0 with sodium hydroxide solution

- Injection volume: 10 μl

- Flow rate: 1.0 mL / min

The dissolution test results of tadalafil are shown in Fig.

As shown in FIG. 5, it was confirmed that the drug was immediately released without being affected by the enteric layer by dispersing tadalafil in water to form a drug layer on the outermost layer of the tablet so that the drug itself had a quick-acting characteristic.

[Test Example 3]

Testosterone dissolution test according to intestinal coating layer content

The tablets of Example 2 (enteric coating layer weight ratio 4.5%) in Table 3 and the tablets of Example 3 (enteric coating layer weight ratio 5.8%) were subjected to a dissolution test under the conditions of pH 4.0 and pH 6.8. The content of the core layers in Examples 2 and 3 is the same.

When the weight ratio of the enteric coating layer to the core layer is less than 3% by weight based on the weight of the core layer in the tablets, the uniformity of the coating layer is lowered. Therefore, when the weight ratio of the enteric coating layer is 3 wt% Respectively.

Example 2 Example 3 Constituent Weight (mg) ratio(%) Weight (mg) ratio(%) Core layer (Raw) Gross weight 132.0 100.0 132.0 100.0 Enteric coating layer Eudragit 4.0 66.67 6.16 80.00 Triethyl citrate 0.5 8.33 0.77 10.00 Hypromellose 1.5 25.00 0.77 10.00 Long coat layer total capacity 6.0 100.0 7.70 100.0 Weight ratio of enteric coating layer to core layer (%) 4.5 5.8

The dissolution test results are shown in Figs. 6 and 7.

As shown in FIG. 6, tablets having a weight ratio of enteric coating layer of about 4.5 wt% at pH 4.0 release about 10% or more of drug until 720 minutes, while tablets having an enteric coating layer weight ratio of about 5.8 wt% Almost no drug was released.

As shown in FIG. 7, the difference in drug release according to the weight ratio of enteric coating layer at pH 6.8 was not large.

[Test Example 4]

Core layer test

A core layer containing etudrosine and a core layer containing ethylcellulose in the testosterone were prepared as shown in Table 4.

Constituent Comparative Example 2 Comparative Example 3 Example 4 Example 5 Weight (mg) ratio
(%) Weight (mg) ratio
(%) Weight (mg) ratio
(%) Weight (mg) ratio
(%) Primary
Granule Tamsulosin hydrochloride 0.2 0.16 0.2 0.16 0.2 0.16 0.2 0.14 Eudragit - - - - 15.0 11.63 25.0 17.99 Ethyl cellulose 7.5 6.17 15.0 11.63 - - - - Mannitol 70.8 58.27 70.8 54.88 70.8 54.88 70.8 50.94 Microcrystalline cellulose 35.0 28.81 35.0 27.13 35.0 27.13 35.0 25.18 After mixing Mannitol 6.0 4.94 6.0 4.65 6.0 4.65 6.0 4.32 Fumaric acid
Stearyl
salt 2.0 1.65 2.0 1.55 2.0 1.55 2.0 1.44 Core layer (Raw)
Gross weight 121.5 100.0 129.0 100.0 129.0 100.0 139.0 100.0

[Comparative Example 2]

0.2 mg of testosterone hydrochloride and 7.5 mg of ethylcellulose were added to ethanol to prepare a binding solution. Thereafter, 70.8 mg of mannitol and 35.0 mg of microcrystalline cellulose were mixed in a high-speed mixer, followed by incorporation of a tamsulosin binding solution to prepare tomosin granules. After coalescence, it was granulated by passing through Co-mil and dried at 50 ° C. The dried material was passed through a Co-mil to formulate it. Step 2 was carried out in the same manner as in Example 1.

[Comparative Example 3]

0.2 mg of tetracycline hydrochloride and 15.0 mg of ethylcellulose were added to ethanol to prepare a binding solution. Thereafter, 70.8 mg of mannitol and 35.0 mg of microcrystalline cellulose were mixed in a high-speed mixer, followed by incorporation of a tamsulosin binding solution to prepare tomosin granules. After coalescence, it was granulated by passing through Co-mil and dried at 50 ° C. The dried material was passed through a Co-mil to formulate it. Step 2 was carried out in the same manner as in Example 1.

[Example 4]

0.2 mg of testosterone hydrochloride and 15.0 mg of Eudragit were added to ethanol to prepare a binding solution. Thereafter, 70.8 mg of mannitol and 35.0 mg of microcrystalline cellulose were mixed in a high-speed mixer, followed by incorporation of a tamsulosin binding solution to prepare tomosin granules. After coalescence, it was granulated by passing through Co-mil and dried at 50 ° C. The dried material was passed through a Co-mil to formulate it. Step 2 was carried out in the same manner as in Example 1.

[Example 5]

0.2 mg of testosterone hydrochloride and 25.0 mg of Eudragit were added to ethanol to prepare a binding solution. Thereafter, 70.8 mg of mannitol and 35.0 mg of microcrystalline cellulose were mixed in a high-speed mixer, followed by incorporation of a tamsulosin binding solution to prepare tomosin granules. After coalescence, it was granulated by passing through Co-mil and dried at 50 ° C. The dried material was passed through a Co-mil to formulate it. Step 2 was carried out in the same manner as in Example 1.

The tablets prepared by the above method were subjected to a dissolution test in the same manner as in Test Example 1 at pH 4.0 with a control as a control agent, commercially available from Daelim Co., Ltd. (0.2 mg of Tamselosin hydrochloride, manufactured by Astellas Pharma Korea).

The results of the dissolution test are shown in Fig.

As shown in FIG. 8, it can be seen that the comparative examples comprising ethylcellulose in the core layer release the drug very rapidly as compared to the reference drug, and those containing the Eudragit in the core layer are similar to the reference drug Indicating a better emission pattern.

[Test Example 5]

Blood concentration of tadalafil and tamsulosin

The tablets of Example 1, diarrhea of Day 1, and senmoderm (Chong Kun Dang, 5 mg of tadalafil) were administered to the human body, and then their blood concentrations were determined.

The maximum blood concentration reaching time (Tmax) for tadalafil was confirmed to be 3 hours for tablets of Example 1 and 4 hours for sentomorphs. Thus, it can be seen that the Tmax of the tablet of Example 1 is faster.

The maximum blood concentration reaching time (Tmax) for the testosterone was confirmed to be 6 hours for tablets of Example 1 and 5 hours for diarrhea of day. Therefore, it can be seen that the Tmax of the tablets of Example 1 is slower.

As a result, it was confirmed that the tablets of the present invention prolonged the drug release of tamsulosin by prolonging the Tmax of the testosterone, thereby confirming that side effects such as orthostatic hypotension can be more effectively reduced.

Claims (17)

A core layer comprising tamsulosin or a pharmaceutically acceptable salt thereof;
An enteric coating layer comprising a nutrient base coating the outside of the core layer; And
A drug coating layer coated on the outside of the enteric coating layer and comprising tadalafil or a pharmaceutically acceptable salt thereof.
2. The pharmaceutical composition of claim 1, wherein the core layer further comprises at least one matrix-type sustained release agent.
3. The composition of claim 2, wherein the matrix-type sustained release agent is selected from the group consisting of methacrylic acid copolymer, methacrylic acid / ethyl acrylate copolymer, methacrylic acid / methyl methacrylate copolymer, hydroxypropylmethylcellulose phthalate and hydroxypropylmethylcellulose Acetate succinate. ≪ RTI ID = 0.0 > 8. < / RTI >
4. The pharmaceutical composition according to claim 3, wherein the matrix type sustained release agent is a methacrylic acid copolymer.
The pharmaceutical composition according to claim 4, wherein the methacrylic acid copolymer is Eudragit.
6. The pharmaceutical composition according to claim 5, wherein the Eudragit is present in an amount of 10 to 20% by weight based on the weight of the core layer.
7. The pharmaceutical composition according to claim 6, wherein the Eudragit is present in an amount of 12 to 18% by weight based on the weight of the core layer.
The pharmaceutical composition according to claim 1, wherein the enteric base is at least one selected from the group consisting of yudrat, zein, shellac, and hydroxypropylmethylcellulose phthalate.
9. The pharmaceutical composition according to claim 8, wherein the enteric base is eudragit.
The pharmaceutical composition according to claim 1, wherein the enteric coating layer further comprises hypromellose and triethyl citrate.
The pharmaceutical composition according to claim 1, wherein the enteric coating layer is contained in an amount of 3 wt% to 10 wt% with respect to the weight of the core layer.
The pharmaceutical composition of claim 1, wherein the drug coating layer further comprises hypromellose.
13. The pharmaceutical composition according to claim 12, wherein the drug coating layer is prepared from a suspension in which tadalafil and hydromellose are dispersed.
14. The pharmaceutical composition according to claim 13, wherein the weight ratio of tadalafil and hypromellose is 1: 0.5 to 1: 1.
A pharmaceutical composition according to any one of claims 1 to 14, wherein the pharmaceutical composition is formulated.
16. The formulation according to claim 15, wherein the preparation is a tablet for oral administration.
A core layer comprising tamsulosin and eudragit;
An enteric coating layer comprising eudragit, triethyl citrate and hypromellose; And
A drug coating layer comprising tadalafil;
≪ / RTI >

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