KR102444073B1 - Pharmaceutical formulation containing methylergometrine maleate with improved stability and method preparing the same - Google Patents

Abstract

The present invention relates to a pharmaceutical preparation containing methylergomethrin maleate having improved stability and a method for preparing the same.
According to the present invention, by including an acidifying agent in the pharmaceutical formulation containing methylergomethrin maleate as the main component, it is possible to minimize the problem that the stability of the main component is reduced due to light, temperature and humidity, and the like. In addition, through the coating of sugar, it is possible to improve the convenience and marketability of taking, and at the same time, it is possible to improve stability.

Description

Methylergomethrin maleate-containing pharmaceutical formulation with improved stability and manufacturing method thereof

The present invention relates to a pharmaceutical preparation containing methylergomethrin maleate having improved stability and a method for preparing the same.

Methylergometrine maleate has a structure of the following formula.

Methyl ergomethrin maleate is known to be effective in preventing and treating bleeding that can occur in childbirth, miscarriage, and uterine dystrophy.

Methyl ergomethrin maleate has a problem of reduced stability in light and temperature and humidity, and development of a pharmaceutical formulation capable of solving this problem is required.

An object of the present invention is to provide a pharmaceutical preparation containing methylergomethrin maleate having stable properties and maintaining a uniform content even under high temperature and high humidity conditions and a method for preparing the same.

Patent Publication No. 10-2019-0089768

The present invention provides a pharmaceutical preparation containing methyl ergomethrin maleate, wherein the pharmaceutical preparation contains methyl ergomethrin maleate, an acidifying agent and a pharmaceutically acceptable additive. A pharmaceutical formulation is provided.

In addition, the present invention provides a tablet prepared by tableting a composition containing methyl ergomethrin maleate and an acidifying agent; And it provides a pharmaceutical formulation comprising a coating layer formed on the tablet surface.

The present invention also provides a method for preparing a pharmaceutical formulation containing methyl ergomethrin maleate, comprising the step of tableting and coating a composition containing methyl ergomethrin maleate and an acidifying agent.

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

In order to solve the above problems, the present invention provides a pharmaceutical preparation containing methyl ergomethrin maleate, the pharmaceutical preparation comprising methyl ergomethrin maleate, an acidifying agent and a pharmaceutically acceptable additive. It provides a pharmaceutical preparation containing methyl ergomethrin maleate.

According to the present invention, by including an acidifying agent in the pharmaceutical preparation containing methyl ergomethrin maleate, which is the main component, the problem that stability of methyl ergomethrin maleate is deteriorated due to light, temperature and humidity, etc. can be minimized.

The pharmaceutical formulation may be formed by tableting wet granules. In one embodiment of the present invention, the granules are preferably wet granules, and dry granulation and direct pressing may cause a problem of content unevenness due to the low content of methyl ergomethrin maleate, which is the main component, and dissolution during tableting. This decrease and the fluidity of the granules may be deteriorated, which may adversely affect the physical properties during tableting.

The pharmaceutical formulation may be prepared by sugar coating and film coating processes.

The acidifying agent may be maleate.

The methyl ergomethrin maleate and the acidifying agent may be present in a weight ratio of 1: 0.8 to 1.6. More preferably, it may be present in a weight ratio of 1:1 to 1:1.4.

The pharmaceutical formulation may contain methyl ergomethrin maleate in an amount of 0.1 to 0.25 mg and an acidifying agent in an amount of 0.05 to 0.3 mg.

By adjusting the weight ratio or amount of methyl ergomethrin maleate and the acidifying agent as described above, a problem in which stability of methyl ergomethrin maleate is deteriorated due to light, temperature and humidity, etc. can be minimized.

The additive may include at least one selected from the group consisting of excipients, binders, disintegrants, glidants, and coating agents.

The excipient may include at least one selected from the group consisting of lactose, microcrystalline cellulose and corn starch.

The binder is selected from the group consisting of povidone, hypromellose, alginic acid, sodium alginate, sodium carboxymethylcellulose, microcrystalline cellulose, powdered cellulose, croscarmellose sodium, crospovidone, pregelatinized starch, sodium starch glycolate and starch. It may include one or more selected from, more preferably, it may be selected from povidone or hypromellose or a mixture thereof.

The disintegrant may be selected from the group consisting of alginic acid, sodium alginate, sodium carboxymethylcellulose, microcrystalline cellulose, powdered cellulose, croscarmellose sodium, crospovidone, pregelatinized starch, sodium starch glycolate and starch, and more Preferably, it may be crospovidone.

The lubricant is calcium stearate, glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, sodium lauryl sulfate, sodium stearyl fumarate, zinc stearate, stearic acid, hardened vegetable oil, polyethylene glycol, benzoic acid It may include at least one selected from the group consisting of sodium, talc and silicon dioxide, and more preferably magnesium stearate.

The coating agent may include at least one selected from the group consisting of hypromellose, titanium oxide, sucrose, talc, polyethylene glycol, glycerin, and carnauba nap.

The methyl ergomethrin maleate and lactose may be present in a weight ratio of 1:150 to 1:250, more preferably 1:180 to 1:220 by weight.

The methyl ergomethrin maleate and microcrystalline cellulose may be present in a weight ratio of 1:540 to 1:600, preferably 1:560 to 1:580 by weight.

The methyl ergomethrin maleate and hypromellose may be present in a weight ratio of 1:4 to 1:12, preferably, in a weight ratio of 1:6 to 1:10.

The methyl ergomethrin maleate and the disintegrant may be present in a weight ratio of 1:4 to 1:12, preferably, in a weight ratio of 1:6 to 1:10.

The methyl ergomethrin maleate and the lubricant may be present in a weight ratio of 1:2 to 1:10, preferably 1:4 to 1:8 by weight.

The pharmaceutical preparation may be a tablet.

According to the present invention, when the pharmaceutical formulation is stored for 4 months under conditions of 40 ± 2 °C and 75 ± 5% relative humidity, the content (weight) of methylergomethrin maleate can be maintained at 98% or more.

In addition, the pharmaceutical formulation according to the present invention is stored for 4 months under 40 ± 2 ° C, 75 ± 5% relative humidity conditions, and then measured in 37 ± 0.5 ° C., tartaric acid solution according to the US Pharmacopoeia (usp) paddle method, as follows The dissolution profile of methyl ergomethrin maleate at the time point after 30 minutes is more than 90%.

In addition, the present invention provides a tablet prepared by tableting a composition containing methyl ergomethrin maleate and an acidifying agent; And it provides a pharmaceutical formulation comprising a coating layer formed on the tablet surface.

The coating layer may include at least one selected from the group consisting of hypromellose, titanium oxide, sucrose, talc, polyethylene glycol, glycerin, and carnauba wax.

In addition, the present invention may provide a method for preparing a pharmaceutical formulation containing methyl ergomethrin maleate, comprising the step of tableting and coating a composition containing methyl ergomethrin maleate and an acidifying agent.

According to the present invention, by including an acidifying agent in the pharmaceutical preparation containing methyl ergomethrin maleate as the main component, it is possible to minimize the problem that the stability of methyl ergomethrin maleate is deteriorated due to light, temperature and humidity, and the like. In addition, it is possible to improve the convenience of taking and marketability through the coating of sugar, and at the same time, it is possible to improve stability.

Hereinafter, the present invention will be described in more detail through examples. Objects, features, and advantages of the present invention will be easily understood through the following examples. The present invention is not limited to the embodiments described herein, and may be embodied in other forms. The embodiments introduced herein are provided so that the spirit of the present invention can be sufficiently conveyed to those of ordinary skill in the art to which the present invention pertains. Therefore, the present invention should not be limited by the following examples.

The present invention minimizes the problem that the stability of methyl ergomethrin maleate is deteriorated due to light, temperature and humidity, etc. by including an acidifying agent in an optimal amount in a pharmaceutical preparation containing methyl ergomethrin maleate as the main component. In addition, the convenience of taking and commercialization were improved through the coating of sugar, and at the same time, stability was also improved.

<Examples and Comparative Examples>

Example composition

purpose of mixing Input raw material name Raw material input (mg) Example 1 Example 2 Example 3 Example 4 Example 5 chief ingredient Methyl ergomethrin maleate 0.125 0.125 0.125 0.125 0.125 acidifying agent maleate 0.15 0.05 0.30 0.15 0.15 excipient lactose hydrate 25 26 25 25 25 Microcrystalline Cellulose 72 72 72 72 72 corn starch binder Povidone K-30 hypromellose 2910 One One One One One disintegrant crospovidone One One One One One lubricant magnesium stearate 0.75 0.75 0.75 0.75 0.75 solvent Purified water 7.5 24 24 24 7.5 solvent ethanol 16.5 16.5 Naked sum 100.025 100.925 100.175 100.025 100.025 coating base hypromellose 2910 9.00 9.00 9.00 9.00 coating base titanium oxide 2.00 2.00 2.00 2.00 coating base white sugar 4.00 4.00 4.00 4.00 coating base talc 3.50 3.50 3.50 3.50 coating base Polyethylene glycol 6000 1.40 1.40 1.40 1.40 coating base concentrated glycerin 0.06 0.06 0.06 0.06 coloring agent Yellow No.203 0.06 0.06 0.06 0.06 coating base carnauba nap 0.04 0.04 0.04 0.04 coating solvent Purified water 112.00 112.00 112.00 112.00 coating base Precipitated Calcium Carbonate coating base gelatin coating base Opadry 85F650007 3.0 Coating base total 3.0 20.06 20.06 20.06 20.06 sum 103.025 120.985 120.235 120.085 120.085

Comparative Example Composition

combination
purpose Input raw material name Raw material input (mg) Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 chief ingredient Methyl ergomethrin maleate 0.125 0.125 0.125 0.125 0.125 0.125 0.125 acidifying agent maleate excipient lactose hydrate 26 26 60 60 60 26 26 Microcrystalline Cellulose 72 72 20 20 20 72 72 corn starch 20 17 17 binder Povidone K-30 3 3 hypromellose 2910 One One One One disintegrant crospovidone One One One One lubricant magnesium stearate 0.75 0.75 0.5 0.5 0.5 0.75 0.75 solvent Purified water 7.5 24 16 7.5 7.5 solvent ethanol 16.5 16 16 16.5 16.5 Naked sum 100.875 100.875 100.625 100.625 100.625 100.025 100.025 coating
gize hypromellose 2910 9.00 9.00 9.00 9.00 9.00 coating
gize titanium oxide 2.00 2.00 2.00 2.00 2.00 2.00 coating
gize white sugar 4.00 4.00 4.00 4.00 4.00 36.00 coating
gize talc 3.50 3.50 3.50 3.50 3.50 3.50 coating
gize Polyethylene glycol 6000 1.40 1.40 1.40 1.40 1.40 - coating
gize concentrated glycerin 0.06 0.06 0.06 0.06 0.06 - coloring agent Yellow No.203 0.06 0.06 0.06 0.06 0.06 0.06 coating
gize carnauba nap 0.04 0.04 0.04 0.04 0.04 0.04 coating
solvent Purified water 112.00 112.00 112.00 112.00 112.00 500.00 coating
gize Precipitated Calcium Carbonate 50.00 coating
gize gelatin 10.00 coating
gize Opadry 85F650007 Coating base total 20.06 20.06 20.06 20.06 20.06 101.6 sum 120.935 120.935 120.685 120.685 120.685 100.025 201.625

Example 1

0.125 mg of methyl ergomethrin maleate, the main components, and 1 mg of hypromellose 2910 were dissolved in 70% ethanol and homogenized. 25 mg of lactose hydrate, 72 mg of microcrystalline cellulose, and 0.15 mg of maleate were blended in a suitable mixer to homogenize. The main ingredient dissolved in 70% ethanol was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 1 mg of crospovidone disintegrant and 0.75 mg of magnesium stearate as lubricant were sieved through a sieve having a mesh size of 600 μM and blended in a mixer to prepare a final composition. The final composition was compressed into tablets with a rotary tableting machine, and 3.0 mg of Opadry 85F650007, a coating base, was dissolved in 70% ethanol and coated as a moisture-proof film coating solution.

Example 2

0.125 mg of methyl ergomethrin maleate, the main components, and 1 mg of hypromellose 2910 were dissolved in purified water and homogenized. 26 mg of lactose hydrate, 72 mg of microcrystalline cellulose, and 0.05 mg of maleate were blended in a suitable mixer to homogenize. The main ingredient dissolved in purified water was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 1 mg of crospovidone disintegrant and 0.75 mg of magnesium stearate as lubricant were sieved through a sieve having a mesh size of 600 μM and blended in a mixer to prepare a final composition. The final composition was compressed into tablets with a rotary tableting machine, and the coating base hypromellose 2910 9 mg, titanium oxide 2 mg, sucrose 4 mg, talc 3.5 mg, polyethylene glycol 6000 1.4 mg, concentrated glycerin 0.06 mg, yellow No. 203 0.06 mg was added to purified water. and dissolved to obtain a coating solution. After the sugar coating, 0.04 mg of carnaubanap was added to light.

Example 3

0.125 mg of methyl ergomethrin maleate, the main components, and 1 mg of hypromellose 2910 were dissolved in purified water and homogenized. 25 mg of lactose hydrate, 72 mg of microcrystalline cellulose, and 0.3 mg of maleate were blended in a suitable mixer to homogenize. The main ingredient dissolved in purified water was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 1 mg of crospovidone disintegrant and 0.75 mg of magnesium stearate as lubricant were sieved through a sieve having a mesh size of 600 μM and blended in a mixer to prepare a final composition. The final composition was compressed into tablets with a rotary tableting machine, and the coating base hypromellose 2910 9 mg, titanium oxide 2 mg, sucrose 4 mg, talc 3.5 mg, polyethylene glycol 6000 1.4 mg, concentrated glycerin 0.06 mg, yellow No. 203 0.06 mg was added to purified water. and dissolved to obtain a coating solution. After the sugar coating, 0.04 mg of carnaubanap was added to light.

Example 4

0.125 mg of methyl ergomethrin maleate, the main components, and 1 mg of hypromellose 2910 were dissolved in purified water and homogenized. 25 mg of lactose hydrate, 72 mg of microcrystalline cellulose, and 0.15 mg of maleate were blended in a suitable mixer to homogenize. The main ingredient dissolved in purified water was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 1 mg of crospovidone disintegrant and 0.75 mg of magnesium stearate as lubricant were sieved through a sieve having a mesh size of 600 μM and blended in a mixer to prepare a final composition. The final composition was compressed into tablets with a rotary tableting machine, and the coating base hypromellose 2910 9 mg, titanium oxide 2 mg, sucrose 4 mg, talc 3.5 mg, polyethylene glycol 6000 1.4 mg, concentrated glycerin 0.06 mg, yellow No. 203 0.06 mg was added to purified water. and dissolved to obtain a coating solution. After the sugar coating, 0.04 mg of carnaubanap was added to light.

Example 5

0.125 mg of methyl ergomethrin maleate, the main components, and 1 mg of hypromellose 2910 were dissolved in 70% ethanol and homogenized. 25 mg of lactose hydrate, 72 mg of microcrystalline cellulose, and 0.15 mg of maleate were blended in a suitable mixer to homogenize. The main ingredient dissolved in 70% ethanol was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 1 mg of crospovidone disintegrant and 0.75 mg of magnesium stearate as lubricant were sieved through a sieve having a mesh size of 600 μM and blended in a mixer to prepare a final composition. The final composition was compressed into tablets with a rotary tableting machine, and the coating base hypromellose 2910 9 mg, titanium oxide 2 mg, sucrose 4 mg, talc 3.5 mg, polyethylene glycol 6000 1.4 mg, concentrated glycerin 0.06 mg, yellow No. 203 0.06 mg was added to purified water. and dissolved to obtain a coating solution. After the sugar coating, 0.04 mg of carnaubanap was added to light.

Comparative Example 1

0.125 mg of methyl ergomethrin maleate, the main components, and 1 mg of hypromellose 2910 were dissolved in 70% ethanol and homogenized. 26 mg of lactose hydrate and 72 mg of microcrystalline cellulose were blended in a suitable mixer to homogenize. The main ingredient dissolved in 70% ethanol was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 1 mg of crospovidone disintegrant and 0.75 mg of magnesium stearate as lubricant were sieved through a sieve having a mesh size of 600 μM and blended in a mixer to prepare a final composition. The final composition was compressed into tablets with a rotary tableting machine, and the coating base hypromellose 2910 9 mg, titanium oxide 2 mg, sucrose 4 mg, talc 3.5 mg, polyethylene glycol 6000 1.4 mg, concentrated glycerin 0.06 mg, yellow No. 203 0.06 mg was added to purified water. and dissolved to obtain a coating solution. After the sugar coating, 0.04 mg of carnaubanap was added to light.

Comparative Example 2

0.125 mg of methyl ergomethrin maleate, the main components, and 1 mg of hypromellose 2910 were dissolved in purified water and homogenized. 26 mg of lactose hydrate and 72 mg of microcrystalline cellulose were blended in a suitable mixer to homogenize. The main ingredient dissolved in purified water was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 1 mg of crospovidone disintegrant and 0.75 mg of magnesium stearate as lubricant were sieved through a sieve having a mesh size of 600 μM and blended in a mixer to prepare a final composition. The final composition is compressed into tablets with a rotary tablet press, and the coating base hypromellose 2910 9mg, titanium oxide 2mg, sucrose 4mg, talc 3.5mg, polyethylene glycol 6000 1.4mg, concentrated glycerin 0.06mg, yellow No.203 0.06mg is added to purified water. and dissolved to obtain a coating solution. After the sugar coating, 0.04 mg of carnaubanap was added to light.

Comparative Example 3

0.125 mg of methyl ergomethrin maleate, the main component, was dissolved in purified water and homogenized. 60 mg of lactose hydrate, 20 mg of microcrystalline cellulose, and 20 mg of corn starch were blended in a suitable mixer to homogenize. The main ingredient dissolved in purified water was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 0.5 mg of magnesium stearate, a lubricant, was sieved through a sieve having a mesh size of 600 uM and blended in a mixer to prepare a final composition. The final composition was compressed into tablets with a rotary tableting machine, and the coating base hypromellose 2910 9 mg, titanium oxide 2 mg, sucrose 4 mg, talc 3.5 mg, polyethylene glycol 6000 1.4 mg, concentrated glycerin 0.06 mg, yellow No. 203 0.06 mg was added to purified water. and dissolved to obtain a coating solution. After the sugar coating, 0.04 mg of carnaubanap was added to light.

Comparative Example 4

0.125 mg of methyl ergomethrin maleate, the main component, was dissolved in ethanol and homogenized. 60 mg of lactose hydrate, 20 mg of microcrystalline cellulose, 17 mg of corn starch, and 3 mg of povidone K-30 were blended in a suitable mixer to homogenize. The main ingredient dissolved in ethanol was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 0.5 mg of magnesium stearate, a lubricant, was sieved through a sieve having a mesh size of 600 uM and blended in a mixer to prepare a final composition. The final composition was compressed into tablets with a rotary tableting machine, and the coating base hypromellose 2910 9 mg, titanium oxide 2 mg, sucrose 4 mg, talc 3.5 mg, polyethylene glycol 6000 1.4 mg, concentrated glycerin 0.06 mg, yellow No. 203 0.06 mg was added to purified water. and dissolved to obtain a coating solution. After the sugar coating, 0.04 mg of carnaubanap was added to light.

Comparative Example 5

0.125 mg of methyl ergomethrin maleate, the main components, and 3 mg of povidone K-30 were dissolved and homogenized. 60 mg of lactose hydrate, 20 mg of microcrystalline cellulose, and 17 mg of corn starch were blended in a suitable mixer to homogenize. The main ingredient dissolved in ethanol was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 0.5 mg of magnesium stearate, a lubricant, was sieved through a sieve having a mesh size of 600 uM and blended in a mixer to prepare a final composition. The final composition was compressed into tablets with a rotary tableting machine, and the coating base hypromellose 2910 9 mg, titanium oxide 2 mg, sucrose 4 mg, talc 3.5 mg, polyethylene glycol 6000 1.4 mg, concentrated glycerin 0.06 mg, yellow No. 203 0.06 mg was added to purified water. and dissolved to obtain a coating solution. After the sugar coating, 0.04 mg of carnaubanap was added to light.

Comparative Example 6

0.125 mg of methyl ergomethrin maleate, the main components, and 1 mg of hypromellose 2910 were dissolved in 70% ethanol and homogenized. 26 mg of lactose hydrate and 72 mg of microcrystalline cellulose were blended in a suitable mixer to homogenize. The main ingredient dissolved in 70% ethanol was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. 1 mg of crospovidone disintegrant and 0.75 mg of magnesium stearate as lubricant were sieved through a sieve having a mesh size of 600 μM and blended in a mixer to prepare a final composition. The final composition was compressed into tablets with a rotary tablet press.

Comparative Example 7

0.125 mg of methyl ergomethrin maleate, the main components, and 1 mg of hypromellose 2910 were dissolved in 70% ethanol and homogenized. 26 mg of lactose hydrate and 72 mg of microcrystalline cellulose were blended in a suitable mixer to homogenize. The main ingredient dissolved in 70% ethanol was added to the homogenized mixture and granulated. The granules were dried and sieved through a sieve having a mesh size of 1.0 mm to form a sized product. Granules were formed by milling through a sieve having a mesh size of 1.0 mm using an oscillating granulator. The final composition was compressed into tablets with a rotary tableting machine, and 2 mg of titanium oxide, 36 mg of sucrose, 3.5 mg of talc, 50 mg of precipitated calcium carbonate, 10 mg of gelatin, and 0.06 mg of Yellow No. 203 were dissolved in purified water to obtain a coating solution. After the sugar coating, 0.04 mg of carnaubanap was added to light.

<Experimental example>

Experimental Example 1

Stability test

In order to evaluate the stability of methyl ergomethrin maleate according to the type of binder by putting the compressed tablets prepared in Examples 2, 5 and Comparative Examples 1 to 3 into an HDPE bottle, accelerated conditions (40° C., 75%), and the content test was performed and shown in Table 3.

Standard: 90.0~110.0% Early 1 month 4 months Example 2 100.4% 100.2% 98.5% Example 5 100.0% 100.1% 100.0% Comparative Example 3 100.1% 99.8% 88.8% Comparative Example 4 100.3% 98.9% 87.9% Comparative Example 5 100.2% 100.1% 93.7%

(In Table 3, 'standard: 90.0~110.0%' indicates the content test standard in the USP Pharmacopoeia methyl ergomethrin tablet section.)

As shown in Table 2, it was shown that the content was suitable in all compositions except Comparative Examples 3 to 5, and the binder content was maintained appropriately in the compositions of Examples 2 and 5 using HPMC.

Experimental Example 2

Stability test

The compressed tablets prepared in Examples 2 to 4 and Comparative Example 2 were put into an HDPE bottle, and accelerated conditions (40° C., 75%) for 4 months to check the stability of the content of methyl ergomethrin maleate according to the ratio of the stabilizer. The content test was carried out under the conditions shown in Table 4.

Standard: 90.0~110.0% Early 1 month 4 months Example 2 100.4% 100.2% 98.5% Example 3 101.2% 99.6% 98.7% Example 4 100.0% 100.1% 100.0% Comparative Example 2 100.3% 98.9% 87.9%

('Standard: 90.0~110.0%' in Table 4 indicates the content test standard in the USP Pharmacopoeia methyl ergomethrin tablet.)

As a result of performing an accelerated test according to the ratio of maleate, Example 4 in which 0.15 mg of maleate was added compared to Comparative Examples 2, 2 and 3 in which 0 mg, 0.05 mg, and 0.3 mg of maleate were added It was confirmed that the compressed tablet of

Experimental Example 3

Dissolution test standard: 70% (Q) or more

The drug dissolution tendency of the tablets prepared in Examples 4 to 5 and Comparative Examples 1 and 2 was observed according to the dissolution test method (paddle method) of the methyl ergomethrin maleate tablet term described in USP. Six tablets of each Comparative Example and Example were tested in 900 mL of 0.5% tartaric acid solution at 75 rpm and 37 ± 0.5 ° C. 30 minutes after the start of the test, 10 mL of the eluate was taken and the filtrate filtered with a membrane filter having a pore size of 0.45 μm was fluoresced. The dissolution rate was calculated by analyzing it with a photometer, and the results are shown in Table 5.

dissolution time
(30 minutes) dissolution rate % Early accelerated 4 months Example 4 95.4±1.5% 93.2±1.7% Example 5 100.8±0.6% 99.2±0.8% Comparative Example 3 98.1±1.2% 85.2±2.9% Comparative Example 4 94.8±0.9% 83.8±3.2%

As a result of the test, the compositions of Comparative Examples 3 to 4 to which the stabilizer was not added showed a result that the dissolution rate decreased and the deviation value increased as the stability test period increased, and the compositions of Comparative Examples 3 to 4 were judged to be unsuitable. In the compositions of Examples 6 to 7 to which maleic acid as a stabilizer was added, the dissolution rates all met the standards. It can be seen that maleic acid must be added to the pharmaceutical formulation containing methylergomethrin maleate to improve stability because the content is maintained under storage conditions only when the stabilizer maleic acid is added and the dissolution rate is not lowered. .

Claims (12)

As a pharmaceutical preparation containing methylergomethrin maleate,
The pharmaceutical preparation includes methyl ergomethrin maleate as a main ingredient; maleate as an acidifying agent; At least one selected from the group consisting of lactose hydrate and microcrystalline cellulose as an excipient; hypromellose as a binder; crospovidone as a disintegrant; magnesium stearate as a lubricant; and at least one selected from the group consisting of purified water and ethanol as a solvent,
The methyl ergomethrin maleate and maleate salts are present in a weight ratio of 1:1 to 1:1.4, and the methylergomethrin maleate and hypromellose are present in a weight ratio of 1:6 to 1:10. A pharmaceutical preparation containing methyl ergomethrin maleate, characterized in that it.
The method according to claim 1,
The pharmaceutical formulation is a pharmaceutical formulation, characterized in that formed by tableting of wet granules.
delete delete delete delete The method according to claim 1,
The methyl ergomethrin maleate and maleate are present in a weight ratio of 1:1 to 1:1.4, wherein the methylergomethrin maleate is selected in an amount ranging from 0.1 to 0.25 mg, and the maleate is from 0.05 to 0.3 A pharmaceutical formulation, characterized in that it is selected from the range of mg.
The method according to claim 1,
When the pharmaceutical formulation is stored for 4 months under conditions of 40 ± 2 °C and 75 ± 5% relative humidity, the content of methylergomethrin maleate is maintained at 98% or more.
The method according to claim 1,
The pharmaceutical formulation is 40 ± 2 ° C., after storage for 4 months under 75 ± 5% relative humidity conditions, 37 ± 0.5 ° C according to the United States Pharmacopoeia (usp) paddle method, when measured in tartaric acid solution, the following dissolution profile showing A pharmaceutical formulation characterized in that:
At the time point after 30 minutes, the dissolution rate of methylergomethrin maleate was more than 90%.
Methyl ergomethrin maleate as a main component; maleate as an acidifying agent; At least one selected from the group consisting of lactose hydrate and microcrystalline cellulose as an excipient; hypromellose as a binder; crospovidone as a disintegrant; magnesium stearate as a lubricant; And a tablet prepared by tableting a composition comprising at least one selected from the group consisting of purified water and ethanol as a solvent; And as a pharmaceutical formulation comprising a coating layer formed on the surface of the tablet,
The methyl ergomethrin maleate and maleate salts are present in a weight ratio of 1:1 to 1:1.4, and the methylergomethrin maleate and hypromellose are present in a weight ratio of 1:6 to 1:10. Characterized in a pharmaceutical formulation.
11. The method of claim 10,
The coating layer is a pharmaceutical formulation comprising at least one selected from the group consisting of hypromellose, titanium oxide, sucrose, talc, polyethylene glycol, glycerin, and carnauba nap.
Methyl ergomethrin maleate as a main component; maleate as an acidifying agent; At least one selected from the group consisting of lactose hydrate and microcrystalline cellulose as an excipient; hypromellose as a binder; crospovidone as a disintegrant; magnesium stearate as a lubricant; And a method for producing a pharmaceutical preparation containing methyl ergomethrin maleate comprising the step of coating after tableting a composition comprising at least one selected from the group consisting of purified water and ethanol as a solvent,
The methyl ergomethrin maleate and maleate salts are present in a weight ratio of 1:1 to 1:1.4, and the methylergomethrin maleate and hypromellose are present in a weight ratio of 1:6 to 1:10. A method for preparing a pharmaceutical formulation containing methylergomethrin maleate, characterized in that