KR100523242B1 - A tablet composition containing ibuprofen - Google Patents

Abstract

The present invention relates to an ibuprofen tablet composition comprising ibuprofen and a water-soluble basic organic compound selected from the group consisting of arginine, lysine, histidine, meglumine and eglumine.

The tablet composition of the present invention is free from problems such as humidity during formulation, and can maintain a continuous and high dissolution rate.

Description

A tablet composition containing ibuprofen

The present invention relates to an improved dissolution property of ibuprofen tablets orally formulated by mixing and tableting ibuprofen with a water-soluble basic compound.

Ibuprofen, a 2- (4-isobutylphenyl) propionic acid, is a well known drug with nonsteroidal, analgesic, anti-inflammatory and antipyretic properties. The drug is a fever and pandemic, including chronic arthritis, arthralgia and arthritis, neuralgia and neuritis, upper respiratory tract, dysmenorrhea, erythema, anti-inflammatory and analgesic, chronic bronchitis, fever, ankylosing erythritis, postoperative pain, myalgia, iron pain and cold Usually 600mg daily dose divided into three doses for cold symptoms. In children, 200 mg for 5-7 years old, 300 mg to 400 mg for 8-10 years old, and 400 mg to 600 mg for 11-15 years old are taken two to three times.

Ibuprofen has such a useful pharmacological effect, but there is a lot of difficulty in formulating because of poor dissolution due to poor solubility of the drug itself. For example, in consideration of the fact that ibuprofen is an acidic substance, Korean Patent Publication No. 99-87084 (99. 12. 15) discloses a formulation method that rapidly disintegrates by adding an inorganic carbonate or bicarbonate, which is an alkaline substance, to dissolve. have. However, such a carbonate-containing formulation reacts with an acidic group of ibuprofen to generate carbon dioxide and water during the formulation process, making it difficult to formulate, and thus, has a problem of increasing humidity and adhesion after formulation.

The present invention is based on the above facts, while the present inventors have studied the manufacturing process of ibuprofen oral formulation which can overcome the disadvantages of the existing formulation and at the same time improve the dissolution rate, while mixing ibuprofen with a water-soluble basic compound and When oral formulation is formulated and found to be able to maintain a continuous and high dissolution rate without problems such as humidity, it has been completed the present invention.

In order to achieve the above object, the present invention provides an ibuprofen tablet composition comprising ibuprofen and at least one water-soluble basic organic compound selected from the group consisting of arginine, lysine, histidine, meglumine and eglumine.

Ibuprofen can be used with all ibuprofen including optical isomers. The particle size of ibuprofen does not significantly affect, but is mainly 5 to 100 µm, preferably 10 to 50 µm. In general, ibuprofen may also comprise 20 to 80%, preferably 40 to 70% in the formulation.

The water-soluble basic organic compound that can be added to the ibuprofen preparation is an essential ingredient for continuously maintaining and improving the dissolution rate of ibuprofen, and any water-soluble basic organic compound that can compensate for the disadvantages of the inorganic carbonate can be used. For example, water-soluble basic amino acids, such as arginine, lysine, and histidine, and basic compounds, such as meglumine, eglumine, and organic amine salt, etc. are mentioned. This component may typically comprise 0.1 to 1.5, preferably 0.25 to 1, by weight relative to ibuprofen 1.

According to the present invention, ibuprofen may be used by being adsorbed onto the water-soluble polymer material in order to further increase the dissolution rate. As the water-soluble polymer material, any one can adsorb poorly soluble ibuprofen to increase the dissolution rate. For example, polyvinylpyrrolidone (povidone), polyethylene glycols, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, gum arabic, gelatin, hydroxyethyl cellulose, poloxamer, carboxyvinyl polymer and the like can be used. This component may typically comprise 0.001 to 0.5, preferably 0.01 to 0.2, by weight relative to ibuprofen 1.

In addition, as a disintegrant which may be added, all disintegrants which are generally used pharmaceutically may be used. For example, sodium starch glycolate, low-substituted hydroxypropyl cellulose, alginic acid, crosslinked polyvinylpyrrolidone, magnesium aluminum silicate, croscarmellose sodium, and the like. Preferred disintegrants may use one or more croscarmellose sodium.

 This component may typically comprise 0.01 to 0.5, preferably 0.01 to 0.3, by weight relative to ibuprofen 1.

 Inert diluents, lubricants and the like may be used as pharmaceutical additives that may be added. As an inert diluent, microcrystalline cellulose, lactose, mannitol, starch, calcium hydrogen phosphate, calcium sulfate and the like can be used.Gluents include stearic acid, magnesium stearate, zinc stearate, talc, magnesium silicate, aluminum aluminum silicate, aluminum metasilicate. Magnesium, light anhydrous silicic acid, hydrogenated vegetable oil and the like can be used.

 These components may typically comprise 0.01 to 0.5, preferably 0.01 to 0.3, by weight relative to ibuprofen 1.

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The ibuprofen formulation of the present invention is prepared by the following method.

It is prepared by mixing ibuprofen with a water-soluble basic organic compound followed by tableting with a disintegrant and other pharmaceutically acceptable additives. In the case where ibuprofen is used by adsorbing the water-soluble high molecular substance, the water-soluble high molecular substance obtained by dissolving the water-soluble high molecular substance in an organic solvent such as water or ethanol or isopropyl alcohol is adsorbed by mixing with ibuprofen; Alternatively, the melt obtained by melting ibuprofen at 60 to 70 ° C. may be adsorbed by mixing with a water-soluble polymer material, and the obtained ibuprofen adsorbate is prepared by mixing with a water-soluble basic organic compound, a disintegrant, and other pharmaceutically acceptable additives. .

Hereinafter, the specific configuration and operation of the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

Example 1.

Ibuprofen 200 mg Povidone 6 mg Talc 6 mg 15 mg of microcrystalline cellulose Croscarmellose sodium 15 mg Arginine 75 mg Crystalline Anhydrous 7 mg Sodium Lauryl Sulfate 2 mg

About ibuprofen Povidone, a water-soluble polymer, is dissolved in water and isopropyl alcohol, and then combined with ibuprofen and dried. Herein, arginine, which is a water-soluble basic organic compound, and a disintegrating agent and other pharmaceutical additives, which are the remaining components, are mixed and prepared.

Example 2.

Ibuprofen 200 mg Povidone 6 mg Talc 6 mg 15 mg of microcrystalline cellulose Croscarmellose sodium 15 mg Arginine 80 mg Crystalline Anhydrous 7 mg Sodium Lauryl Sulfate 2 mg

It is prepared in the same manner as in Preparation Example 1, followed by tableting.

Example 3.

Ibuprofen 200 mg Polyethylene glycol6000 10 mg Talc 15 mg 15 mg of microcrystalline cellulose Croscarmellose sodium 15 mg Arginine 70 mg Crystalline Anhydrous 7 mg Sodium Lauryl Sulfate 2 mg

It is prepared in the same manner as in Preparation Example 1, followed by tableting.

Example 4.

Ibuprofen 200 mg Talc 5 mg 15 mg of microcrystalline cellulose Croscarmellose sodium 15 mg Arginine 100 mg Crystalline Anhydrous 7 mg Sodium Lauryl Sulfate 2 mg

Ibuprofen and a water-soluble basic organic compound and a disintegrant and other pharmaceutical additives are mixed and fired to obtain a product.

Example 5.

Ibuprofen 400 mg Polyethylene Glycol6000 20 mg Talc 20 mg 40 mg of microcrystalline cellulose Croscarmellose sodium 40 mg Arginine 120 mg Crystalline Anhydrous 6 mg Sodium Lauryl Sulfate 4 mg

It is prepared in the same manner as in Preparation Example 1, followed by tableting.

Example 6.

Ibuprofen 400 mg Talc 12 mg 40 mg of microcrystalline cellulose Croscarmellose sodium 40 mg Meglumine 120 mg Crystalline Anhydrous 6 mg Sodium Lauryl Sulfate 5 mg

It is prepared in the same manner as in Preparation Example 4, followed by tableting.

Example 7.

Ibuprofen 400 mg Povidone 15 mg Talc 12 mg Microcrystalline cellulose 30 mg Croscarmellose sodium 30 mg Meglumine 150 mg Crystalline Anhydrous 8 mg Sodium Lauryl Sulfate 5 mg

It is prepared in the same manner as in Preparation Example 1, followed by tableting.

Comparative Example 1.

Ibuprofen 200 mg Talc 6 mg 15 mg of microcrystalline cellulose Croscarmellose sodium 15 mg Crystalline Anhydrous 7 mg Sodium Lauryl Sulfate 2 mg

It is prepared in the same manner as in Preparation Example 4, followed by tableting.

Comparative Example 2.

Ibuprofen 200 mg Anhydrous sodium carbonate 15 mg Microcrystalline Cellulose 60mg Croscarmellose sodium 15 mg 0.8 mg of silicon dioxide Stearic acid 3 mg

It is prepared in the same manner as in Preparation Example 4, followed by tableting.

Experimental Example Comparative dissolution test

The tablets prepared in Examples 1 and 4 and Comparative Examples 1 and 2 were eluted after 10, 15, 30, 60, and 120 minutes of elution according to the Dissolution Test Method 2 (paddle method) of the general test method of the Pharmacopoeia. The amount was measured according to the following conditions.

     Dissolution Test Equipment: Erweka DT 80

     Eluent: 900 ml of water

     Eluent temperature: 37 ± 0.5 ℃

     Rotational Speed: 50 rpm

     Assay: Liquid Chromatography

Column: Cosmosil C ₁₈ (150㎜ × 4.6㎜)

                     Mobile phase: Acetonitrile: 1% chloride acetic acid (pH 3.0) (65: 35)

                     Flow rate: 1.2 ml / min

                     Detector: UV 254 nm

                     Injection amount: 20µl

As can be seen from the results shown in Table 1, the preparation of Example 1 according to the present invention by the addition of a water-soluble polymer and a water-soluble basic organic compound significantly increased dissolution compared to Comparative Example 1 to increase the solubility of poorly soluble ibuprofen. It could be confirmed, and since the manufacturing process is easier than the existing known literature provides a clear advance in the art.

Comparative Dissolution Test Result (Unit: Dissolution Rate%) Sample time 10 minutes 15 minutes 30 minutes 60 minutes 120 minutes Example 1 32% 50% 62% 76% 84% Example 4 35% 52% 64% 78% 85% Comparative Example 1 7% 10% 13% 18% 24% Comparative Example 2 25% 45% 62% 75% 83%

As described above and it can be seen through the examples, the ibuprofen tablet composition of the present invention has no problems such as humidity when formulated, there is an effect that can maintain a continuous high dissolution rate.

Claims (9)

Ibuprofen, and at least one water-soluble basic organic compound selected from arginine, lysine, histidine, meglumine and eglumine, wherein ibuprofen is selected from polyvinylpyrrolidone (povidone), polyethylene glycols, hydroxypropyl cellulose, Ibuprofen tablet composition adsorbed on at least one water-soluble high molecular material selected from the group consisting of hydroxypropylmethylcellulose, gum arabic, gelatin, hydroxyethylcellulose, poloxamer and carboxyvinyl polymer. delete The method of claim 1, Ibuprofen tablet composition comprising a water-soluble basic organic compound in a ratio of 0.1 to 1.5 by weight relative to ibuprofen 1. The method of claim 1, Ibuprofen tablet composition comprising a water-soluble polymer material in a ratio of 0.001 to 0.5 by weight relative to ibuprofen 1. delete delete delete (i) ibuprofen selected from the group consisting of polyvinylpyrrolidone (povidone), polyethyleneglycols, hydroxypropylcellulose, hydroxypropylmethylcellulose, gum arabic, gelatin, hydroxyethylcellulose, poloxamer and carboxyvinyl polymer Adsorbing by mixing with a solution of water or an organic solvent of at least one water-soluble high molecular material, and (ii) at least one water-soluble basic selected from the group consisting of ibuprofen and arginine, lysine, histidine, meglumine and eglumine A method for producing a ibuprofen tablet composition comprising the step of mixing and tableting an organic compound. The method of claim 8, The ibuprofen is a molten ibuprofen.