KR20090047310A - Multi-layered tablet containing dexibuprofen - Google Patents

Abstract

       The present invention relates to a multilayer tablet comprising a dexibuprofen as an active ingredient, an immediate release layer comprising a desiccant and a fast-release excipient, and a sustained release layer comprising a desiccant and a release control agent, wherein the total content of dexibuprofen is preferred. Preferably, 300 mg, 90-130 mg of the immediate release layer and 170-210 mg of dexibuprofen are contained in the sustained-release layer to satisfy both high initial blood levels and sustained effective blood levels, as well as administration twice a day. The present invention relates to a dexibuprofen-containing multilayer tablet.

Description

Multi-layered tablet containing dexibuprofen {MULTILAYERED TABLET CONTAINING DEXIBUPROFEN}

The present invention relates to a multilayer tablet comprising a dexibuprofen as an active ingredient, an immediate release layer comprising a desiccant and a fast-release excipient, and a sustained release layer comprising a desiccant and a release control agent, wherein the total content of dexibuprofen is preferred. Preferably, 300 mg, 90-130 mg of the immediate release layer and 170-210 mg of dexibuprofen are contained in the sustained-release layer to satisfy both high initial blood levels and sustained effective blood levels, as well as administration twice a day. The present invention relates to a multilayer tablet containing dexibuprofen possible.

Ibuprofen (Ibuprofen) is a representative drug of non-steroidal antiinflammatory drugs (NSAIDs), which are excellent in safety and efficacy.Ibuprofen inhibits the activity of cyclooxygenase and prostaglandin. It has been widely used in the treatment of rheumatoid arthritis, arthralgia, gout, ankylosing spondylitis and related diseases, and postoperative analgesia and anti-inflammatory due to trauma.

In addition, ibuprofen is commercially available for rapid release and sustained release formulations. The rapid release formulation contains 100 to 600 mg of ibuprofen in one tablet, and 200 to 600 mg is divided into 3 to 4 times daily. Oral, up to 3,200 mg per day, sustained-release preparations include Brufen Retard ^® (Boots Pharmaceuticals), 800 tablets of ibuprofen per tablet, 1 day 1 It is to be given two tablets per time.

Ibuprofen is usually present in the form of racemates in which two stereoisomers of (R) and (S) are mixed in a ratio of 1: 1. Double (R) sieves are converted to (S ) sieves in vivo to show efficacy. Therefore, the formulation consisting of (S) -Ibuprofen alone, which is an optically active pharmacologically active, can be expected to have an effective pharmacological effect at a relatively small dose, and is also sensitive to accumulation of pharmacologically inactive (R) bodies during long-term administration. Concerns about side effects such as hypersensitivity can be completely ruled out.

Reported studies of effective blood concentrations of dexibuprofen are scarce and are usually based on the effective blood concentration of ibuprofen. Pharmacodynamic studies conclude that dexibuprofen: ibuprofen = 0.5: 1. According to the Wyeth data, the effective blood concentration of ibuprofen is (EC50) 6-10µg / ml, so the effective blood concentration of dexibuprofen is 3-5µg / ml, and less than 20% of patients. The concentration showing the pain relief effect may be estimated to be 1 to 10 µg / ml for ibuprofen and 0.5 to 5 µg / ml for dexibuprofen. (Reference [1]: /briefing/3882B2_04_Wyeth-Ibuprophen.doc, [2]: Fakhreddin Jamali, Cornelia M. Kunz-Dober.Pain-mediated altered absorption and metabolism of ibuprofen: an explanation for decreased serum enantiomer concentration after dental surgery Br J Clin Pharmacol, 1999; 47: 391-396)

Dexibuprofen ((S) - (+) -Ibuprofen) is an (S) optical isomer of ibuprofen, a bitter-white crystalline powder with the following structure, hardly soluble in water: to be.

Dexibuprofen oral tablets that are currently commercialized contains 300 mg of dexibuprofen, one tablet orally 3 to 4 times daily, and up to 1,200 mg daily, but commercialized There is no sustained release preparation.

Dexibuprofen is composed of the active agent of ibuprofen has relatively low dosage and side effects, and thus has the advantage of reducing the dosage unit to facilitate taking, but due to the very low melting point (about 52 ℃) handling difficulties and The active ingredient is melted by the heat generated during compression into tablets for oral administration, which causes difficulties in production such as capping and sticking.

WO 95/01781 describes a multi-dose oral tablet comprising a nonsteroidal anti-inflammatory material. The patent is a bilayer tablet comprising 800 mg of ibuprofen as the active ingredient, which contains 250 mg of active ingredient in the immediate release portion and 550 mg of the active ingredient in the sustained release portion. The fast-release part is mixed with the active ingredient and corn starch, granulated with methyl cellulose aqueous solution, dried through a sieve to obtain homogeneous particles, and then cross-linked polyvinylpyrrolidone is added and corn starch and carboxymethyl It is obtained by mixing starch and magnesium stearate. The sustained release portion is mixed with an appropriate amount of ibuprofen with mannitol and hydroxypropylmethyl cellulose, granulated with polyvinylpyrrolidone alcohol solution, dried through a sieve to obtain homogeneous particles, and then talc, magnesium stearate and colloidal. It is prepared by mixing silica. It describes that the granules obtained are put into a first loading hopper and a second loading hopper, respectively, and compressed to produce a bilayer tablet of ibuprofen.

International Patent Publication No. WO 94/10993 describes the pharmaceutical compositions characteristic of (S) - (+) -ibuprofen in ibuprofen. In the case of this patent, the granules are prepared using a pharmaceutically acceptable water soluble binder containing 40-70% (w / w) (S) - (+) -ibuprofen as active ingredients and excluding polyvinylpyrrolidone. After preparation, a method of producing rapid-release tablets by mixing less than 2% (w / w) silica is disclosed.

U.S. Patent No. 5,869,102 discloses a rapid-release tablet in which the active ingredient contains dexibuprofen, a microcrystalline cellulose as a diluent, and colloidal silica as a disintegrant, by a direct method. It is described.

In addition, US Pat. No. 5,631,296 discloses a material selected from 90.0 to 99.9% (w / w) of (S) - (+) -ibuprofen and inorganic salts, dilute alkali metal chlorides and mixtures thereof. It describes a pellet formulation of (S) - (+) -ibuprofen comprising a. In the case of the patent, in the embodiment for the delayed-release of the active ingredient (Ethyl acrylate) for coating the pellets using ethyl acrylate (Ethyl acrylate), the sustained release of (S) - (+) -ibuprofen to fill the capsule Sex pellet capsule formulations are described.

However, the compositions according to the patents have the disadvantage of having to take a high dose of 3 to 4 times a day, ibuprofen and dexibuprofen have a very low melting point in the manufacture of tablets currently used in the manufacture of tablets without a separate device such as a cooler When compressed into tablets by production technology, problems such as capping and sticking occur, which requires a large amount of excipients, and the dosage unit of the active ingredient must be large to indicate an effective blood concentration.

Therefore, an object of the present invention is characterized by a multi-layered tablet consisting of an immediate release layer and a sustained release layer containing dexibuprofen as an active ingredient, and greatly improves tableting performance as compared to conventional formulations. It is to provide a dexibuprofen-containing multi-layered tablet that can be administered twice a day as well as to be administered four times-to maintain a rapid initial effective blood concentration and maintain a sustained effective blood concentration.

In order to achieve the above object, the present invention is an immediate release layer comprising a dexibuprofen, a drying agent and a fast-acting excipient; And it provides a dexibuprofen-containing multilayer tablet consisting of a sustained release layer comprising a dexibuprofen, a drying agent and a release control agent.

The multi-layer oral tablet consisting of a rapid release portion and a sustained release portion according to the present invention is not only administered orally to give an immediate therapeutic effect, but also keeps a constant concentration in the plasma for an active ingredient for a considerable time, It is very useful because it can not only reduce the number of drugs, but also increase the drug compliance to patients, thereby increasing the compliance with the medication.

The present invention relates to a multilayer tablet comprising a dexibuprofen as an active ingredient, an immediate release layer comprising a desiccant and a fast-release excipient, and a sustained release layer comprising a desiccant and a release control agent, wherein the total content of dexibuprofen is preferred. Preferably, 300 mg, but the immediate release layer is 90 to 130 mg, the sustained release layer contains 170 to 210 mg of dexibuprofen to satisfy both high initial blood levels and sustained effective blood levels, as well as twice a day The present invention relates to a dexibuprofen multilayer tablet that can be administered.

Hereinafter, the components of the multilayer tablet of the present invention will be described in more detail.

(1) dexibuprofen

The active ingredient of the present invention is dexibuprofen, a nonsteroidal anti-inflammatory agent that is highly effective in the treatment of rheumatoid arthritis, and the like. A pharmaceutically acceptable salt of dexibuprofen, for example, zinc salt, calcium salt, alginate salt or li thereof Contains nephritis.

(2) desiccant

The desiccant used in the present invention may be selected from light silicic anhydride, hydrotalcite, aluminum magnesium silicate, aluminum hydroxide, aluminum silicate, magnesium aluminum metasilicate.

In particular, these desiccants provide convenience in the production process by reducing capping and sticking, etc., which occur due to the melting of the active ingredient by heat that can occur when compressed into tablets. At this time, the adsorbent may be added after the heating, melting of the active ingredient so that the weight ratio of the active ingredient: the adsorbent is 1: 0.01 ~ 3, preferably 1: 0.1 ~ 2.

(3) fast-acting excipients

In the present invention, in order to quickly elute the drug of the immediate release layer, to facilitate granulation, and to enhance the binding force when compressed into tablets, a sugar alcohol, a water-soluble polymer, an oily base or a mixture thereof may be further included. At this time, it is preferable to use a sugar alcohol, a water-soluble polymer, an oil-based base or a mixture thereof with respect to the active ingredient in a weight ratio of 1: 0 to 2.

The sugar alcohols usable in the present invention are selected from the group consisting of xylitol, solititol, mannitol and mixtures thereof, and the water-soluble polymer is hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, polyethylene glycol, polyethylene oxide, Polyvinyl alcohol and mixtures thereof, the oleaginous base is composed of sucrose fatty acid ester, glyceryl behenate, glyceryl parito stearate, glyceryl monooleate, glyceryl monostearate and mixtures thereof It can be selected from the group.

(4) sustained release carrier

Sustained release carriers for sustained and constant release of active ingredients in sustained-release tablets of the present invention include polyethylene oxide with a molecular weight of 10,000 to 9,000,000, hydroxypropylmethyl cellulose with a molecular weight of 1,000 to 4,000,000, and hydroxypropyl cellulose with a molecular weight of 2,000 to 2,000,000 , Carboxyvinyl polymer, polyvinyl alcohol, xanthan gum, guar gum, locust bean gum, carboxymethyl cellulose and its derivatives, methyl cellulose and its derivatives, and povidone-polyvinylacetate copolymer, The solid dispersion and the sustained release carrier may be used in a weight ratio of 1: 0.01-3, preferably in a weight ratio of 1: 0.05-2.

(5) multilayer tablets

Multi-layered tablet according to the present invention is composed of the immediate release layer and the sustained release layer, in the immediate release layer of tablets 90 to 130mg, the sustained release layer to contain 170 to 210mg of dexibuprofen, more preferably in the immediate release layer Make sure to include 110 mg of dexibuprofen in the 110-mg, slow-release layer. At this time, the sum of the immediate release layer and the sustained release layer is 260 to 340 mg, most preferably 300 mg.

As a representative example of the present invention, when preparing a bilayer tablet consisting of an immediate release layer and a sustained release layer, a multi-layer tablet may be prepared by primary tableting the immediate release layer and then filling the sustained release layer thereon to perform secondary tableting. have. At this time, after tableting the immediate release layer, tableting of the sustained release layer is not necessarily performed, and tableting of the sustained release layer is preferentially performed, and it is also possible to fill and tablet the granules of the immediate release layer. In addition, the immediate release layer and the sustained release layer may be filled in a sequential order or in reverse order, respectively.

In addition, the multilayer tablet of the present invention may be prepared as a single-layer tablet having both immediate release and sustained release properties, including a three-layer tablet consisting of an immediate release layer and a sustained release layer, and a mixed composition of the immediate release layer composition and a sustained release layer composition. In addition, after the sustained release layer is prepared as a nucleus, it may also be prepared as a multi-tablet containing a sustained release core (Core) surrounded by an immediate release layer.

According to the present invention, a multi-layer tablet consisting of a fast-release portion and a slow-release portion containing the same active ingredient is 100 revolutions per minute using 900 ml of artificial intestinal fluid (KKP 8, Disintegration Test 2, pH 6.8) as an eluent. When the dissolution test is carried out by the paddle method of Korea (the eighth amendment of the KP, the dissolution test method 2), 35 to 55% after 1 hour of dissolution test, 35 to 65% after 3 hours, and 80% or more after 24 hours Should be.

The multi-layered tablet of the present invention has the advantage that the rapidly released active ingredient allows the plasma concentration to reach the minimum effective therapeutic concentration quickly, and the delayed released active ingredient maintains the effective blood concentration continuously for the planned time. Dosage and frequency of administration can be dramatically reduced, which is very pharmaceutically useful.

 (A) Immediate release

The immediate release layer of the present invention comprises the dexibuprofen, a desiccant, and a fast-acting excipient. The immediate release layer of the present invention can be prepared by compressing the composition in the form of a tablet, which allows the initial drug to be released quickly to reach the effective therapeutic concentration of the active ingredient.

(B) Western Floor

The sustained release layer of the present invention includes the above dexibuprofen, a desiccant and a release controlling agent, and may further include a pharmaceutically acceptable excipient.

The sustained release layer of the present invention can be prepared by compressing the composition in the form of a tablet, and allows the active ingredient to maintain a uniform release rate over a long time.

(C) pharmaceutically acceptable excipients

The present invention may further include a pharmaceutically acceptable excipient for maintaining the dosage form and hardness of the appropriate tablet.

Excipients can be used as long as they are commonly used in the pharmaceutical field, and representative examples are crosslinked polyvinylpyrrolidone, crosslinked carboxymethyl cellulose sodium, carboxymethyl starch, methacrylate-divinylbenzene air Coated calcium, polyvinyl alcohol, lactose, microcrystalline cellulose and cellulose derivatives, starch and derivatives thereof, cyclodextrins and dextrin derivatives, pregelatinized starch and derivatives thereof, light silicic anhydride, magnesium stearate, glyceryl monostearate Sodium stearyl fumarate, talc or hydrogenated castor oil and the like can be used.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

<Production of Solid Dispersion>

Example 1

After dissolving 300.0 g of dexibuprofen (Dr. Lady's Lab), 60.0 g of hard silicic anhydride (Degussa) was slowly added while stirring, followed by stirring for about 45 minutes to achieve homogeneous dispersion (see Table 1). . When the dispersion was made homogeneously, the solid dexibuprofen dispersion aggregate was prepared by cooling to room temperature with continuous stirring. The prepared aggregate was cooled at room temperature by cold air (30 ° C.) for about 2 hours, pulverized with a high speed grinder, and sieved through a No. 20 (850 μm) sieve to prepare a solid dispersion.

Example 2

A solid dispersion was prepared in the same manner as in Example 1, except that 90.0 g of hard silicic anhydride was used.

Example 3

A solid dispersion was prepared in the same manner as in Example 1, except that 110.0 g of hard silicic anhydride was used.

Example 4

After preheating the all-purpose mixer to about 95 ° C, 300.0 g of dexibuprofen and 50.0 g of xylitol (cahuahua Kang Pharmaceutical Co., Ltd.) were added and melted, followed by slowly adding 60.0 g of hard silicic anhydride while stirring, and then about 45 Stirring for minutes allowed the dispersion to be homogeneous. Thereafter, a solid dispersion was prepared in the same manner as in Example 1.

Example 5

A solid dispersion was prepared in the same manner as in Example 4, except that 20.0 g of hydroxypropylmethyl cellulose (Dow Chemical) was used instead of 50.0 g of xylitol of Example 4 and hydroxypropylmethyl cellulose was dispersed.

<Production of immediate release layer>

Example 6

To 10.3 mg of the solid dispersion (dexicbuprofen content: 110 mg per limit) obtained from Example 3 according to the composition of Table 2, 8.4 mg of talc (Nippon Talc), a lubricant, was mixed firstly for 5 minutes, Pharmaceutically acceptable excipients are 7.4 mg of lactose (DMV International), 36.4 mg of microcrystalline cellulose (PMC Biopolymer), 2.7 mg of crosslinked carboxymethyl cellulose (DMV International) and 3.7 mg of hard silicic anhydride. The mixture was mixed for 2 minutes for 60 minutes and compressed to a hardness of about 8 to 12 kp to prepare a rectangular immediate release tablet.

Examples 7-10

After the first mixing according to the composition of Table 2, the immediate release layer tablets were prepared in the same manner as in Example 6 except that the pharmaceutically acceptable excipient was added and the second mixture.

<Preparation of Sustained Release Tablet>

Examples 11-14

The sustained-release tablet was prepared in the same manner as in Example 6, except that the solid dispersion and the lubricant according to the composition of Table 3 were first mixed, and then the release regulator was added and the mixture was secondary.

Examples 15,16 and Comparative Examples 1,2 : Preparation of bilayer tablet consisting of immediate release layer and sustained release layer

The second-layer tablets were prepared by mixing the immediate release layer components according to the composition shown in Table 4 below, followed by primary tableting with a hardness of about 2 to 3 kp, followed by secondary tableting with a hardness of about 8 to 12 kp. .

Test Example 1 : Pharmacodynamic Equivalence Test (1)

Example 15 of the bi-layer tablet and deck bitter Pro which is commercially available as a pen tablet Dax Pen ^® (dexibuprofen as a 300 mg tablet, Binex G) divided by the military 12 kill Group 2 to evaluate the pharmacodynamic equivalence of the tablet 24 healthy For the volunteers, a two-way crossover pharmacokinetic equivalence test divided into stages 1 and 2 was conducted under the following conditions, and the results are shown in Table 5 and FIG. 1.

<Test conditions>

Specimen: Example 15 and Daxpen ^® Tablets

Subjects by group: 24 persons in 2 groups, 12 persons per group

Dosing: Group 1 of the first dosing group received two tablets of the bilayer tablet of Example 15 (600 mg as dexibuprofen) with the start of the trial, and group 2 received daxpen ^® 1 tablet (300 mg as dexibuprofen). ) Was dosed with the start of the test and 6 hours later Daxfen ^® 1 tablet (300 mg as dexibuprofen) was dosed again. After a period of drug suspension, the second dose group was administered in the same manner as the first dose, except that the first and second dose tablets were crossed.

As shown in Table 5 and FIG. 1, the pharmacodynamic equivalence test results of the Daxfen ^® tablets commercially available as double-layered tablets and dexibuprofen tablets of Example 15 showed that the two formulations had pharmacodynamic equivalent efficacy at 90% confidence intervals. It was shown to express.

Test Example 2 : Multi Simulation

Based on the pharmacokinetic equivalence test results of the commercial daxpen ^® tablets as Example 15 bilayer tablets and dexibuprofen tablets of Test Example 1, a simulation was performed for 72 hours of repeated administration and the results are shown in Table 6 and FIG. 2 is shown.

Many medications require repeated dosing regimens in order to have a lasting therapeutic effect. These dosing regimens must maintain adequate blood levels without excessive fluctuations in the blood and accumulation of drugs. Thus, as shown in Table 6 and FIG. 2 above, simulation of 72 hours of repeated dosing based on the pharmacokinetic equivalence test results of the commercial daxpen ^® tablets as bilayer tablets and dexibuprofen immediate release tablets of Example 15 The results showed that both formulations have a sustained effect even after repeated administration without drug accumulation.

Test Example 3 Pharmacodynamic Equivalence Test (2)

In order to evaluate the pharmacodynamic profile of the double-layered tablets of Comparative Examples 1 and 2, a 2-way cross-pharmacodynamic test divided into stages 1 and 2 was performed on 24 healthy volunteers divided into 2 groups of 12 persons per group, under the following conditions. , The results are shown in Table 7 and FIG. 3.

<Test conditions>

Specimens: Comparative Example 1 and Comparative Example 2

Subjects by group: 24 persons in 2 groups, 12 persons per group

Dosing: Group 1 of the first dose group was administered two tablets (600 mg as dexibuprofen) of Comparative Example 1, group 2 of two tablets of Comparative Example 2 (600 mg as dexibuprofen) Was administered with the start of the test. After a period of drug suspension, the second dose group was administered in the same manner as the first dose, except that the first and second dose tablets were crossed.

As shown in Table 7 and Figure 3, Comparative Example 1 showed a phenomenon that the blood concentration rises rapidly and C _max is significantly high, but falls below the minimum effective blood concentration before 8 hours. Comparative Example 2 was maintained for more than 12 hours, but it is judged to be inadequate for anti-inflammatory analgesics that have low initial blood concentrations and therefore require rapid drug expression.

Test Example 4 : Dissolution test of immediate release tablets

The dissolution test was carried out using the immediate release layer tablets prepared in Examples 6 to 10 under the following conditions based on the method for setting the rapid release drug of the Korean Food and Drug Administration 『Guidelines for Establishing Elution Standards for Oral Drugs』. It is shown in Table 8 and FIG.

<Test conditions>

Specimens: Immediate layer tablets of Examples 6 to 10

Dissolution Test Solution: 900 ml, 37 ㅁ 0.5 ℃

Dissolution method: Method 2, paddle method, KEPA, 50 revolutions per minute

As shown in Table 8 and FIG. 4, all of the rapid-release layer tablets prepared in Examples 6 to 10 exhibit a rapid dissolution rate of 85% or more within 1 hour after the start of dissolution, so that the solid dispersion of the present invention is used as an active ingredient. An antiseptic tablet is suitable for expressing a quick drug.

Test Example 5 : Dissolution Test of Sustained Release Tablet

The dissolution test was performed under the following conditions using the sustained release tablets prepared in Examples 11 to 14, and the results are shown in Table 9 and FIG. 5.

<Test conditions>

Specimen: Sustained-Release Tablets of Examples 11-14

Dissolution Test Solution: 900 ml, 37 ㅁ 0.5 ℃

Dissolution Method: Method 2 of the Pharmacopoeia dissolution test (paddle method), 100 revolutions per minute

As shown in Table 9 and Figure 5, the sustained-release tablet prepared in Examples 11 to 14 slowly eluted the active ingredient in the sustained-release layer portion for 12 hours.

Test Example 6 : Dissolution test of bilayer tablets (1)

Dissolution test was carried out under the following conditions using bilayer tablets prepared in Examples 15, 16 and Comparative Example 2. The results are shown in Table 10 and FIG. 6.

<Test conditions>

Specimens: bilayer purification of Examples 15, 16 and Comparative Example 2

Dissolution Test Solution: 900 ml, 37 ㅁ 0.5 ℃

Dissolution Method: Method 2 of the Pharmacopoeia dissolution test (paddle method), 100 revolutions per minute

As shown in Table 10 and FIG. 6, the bilayer tablets prepared in Examples 15 and 16 were continuously eluted for 24 hours after the initial dissolution rate was rapidly increased and 25 to 55% after 1 hour and 35 to 65 after 3 hours. Elution criteria of at least 80% at 24% and 24 hours were met. On the other hand, Comparative Example 2 did not meet the dissolution criteria of 1 hour, which is consistent with the pattern shown in the pharmacodynamic profile.

Test Example 7 : Dissolution Test by Paddle Rotation for Two-Layer Tablet

The dissolution test was performed under the following dissolution conditions using the bilayer tablet of Example 16, and the results are shown in Table 11 and FIG. 7.

<Test conditions>

Specimen: Bilayer Purification of Example 16

Dissolution Test Solution: 900 ml, 37 ㅁ 0.5 ℃

Dissolution Method: Method 2, Paddle Method

As shown in Table 11 and Figure 7, the dissolution test results for each rotation speed can be expressed quickly rapid elution for the initial 1 hour, regardless of the rotational speed, after which the elution is gradually continued to show a continuous drug efficacy A stable emission pattern was shown.

The multi-layer oral tablet consisting of a rapid release portion and a sustained release portion according to the present invention is not only administered orally to give an immediate therapeutic effect, but also keeps a constant concentration in the plasma for an active ingredient for a considerable time, It is very useful because it can not only reduce the number of drugs, but also increase the drug compliance to patients, thereby increasing the compliance with the medication.

1 is a graph showing the embodiment 15 and Dax Pen ^® defined pharmacodynamic equivalence test results,

2 is a graph showing Example 15 and the Daxpen ^® defined multi-simulation results,

3 is a graph showing the pharmacokinetic equivalence test results of Comparative Example 1 and Comparative Example 2,

4 is a graph showing the dissolution test results of the tablet including the rapid release portion prepared in Examples 6 to 10,

Figure 5 is a graph showing the dissolution test results of the sustained-release tablet consisting of a sustained release portion prepared in Examples 11 to 14,

Figure 6 is a graph showing the dissolution test results of the bilayer tablet consisting of the fast-release portion and the slow-release portion prepared in Examples 15, 16 and Comparative Example 2,

7 is a graph showing the dissolution test results according to the number of paddle rotation of the tablet prepared in Example 16.

Claims (7)

Immediate release layer comprising dexibuprofen, a desiccant, and a fast-acting excipient; And Consisting of a sustained release layer containing dexibuprofen, a desiccant and a release control agent Dexibuprofen-containing multilayer tablets. The method of claim 1, Dexibuprofen-containing multilayer tablet, characterized in that administered twice a day. The method according to claim 1 or 2, A dexibuprofen-containing multilayer tablet comprising a total of dexibuprofen contents of the immediate release layer and the sustained release layer at 300 mg. The method according to any one of claims 1 to 3, Dexibuprofen multi-layer tablets, characterized in that contained in the rapid release portion 90 to 130mg, 170-210mg in the slow release portion of tablets tablets. The method according to any one of claims 1 to 5, Multi-layer tablets consist of two-layered tablets in the fast-release section and the slow-release section and under the test conditions of the Korean Pharmacologic Elution Test No. 2 (paddle method), the Korean Pharmacopeia Disintegration Test No. 2 solution (pH6.8 artificial intestinal fluid) and 100 revolutions per minute Dexibuprofen-containing multilayer tablets, characterized in that the dissolution rate of 35% to 55% after 1 hour, 35% to 65% after 3 hours and 80% or more at 24 hours. The method of claim 1, A dexibuprofen-containing multilayer tablet, wherein the desiccant is selected from hard silicic anhydride, hydrotalcite, aluminum magnesium silicate, aluminum hydroxide, aluminum silicate, and magnesium aluminum metasilicate. The method of claim 1, Release regulators include polyethylene oxides with molecular weights of 10,000 to 9,000,000, hydroxypropylmethyl celluloses with molecular weights of 1,000 to 4,000,000, hydroxypropyl celluloses with molecular weights of 2,000 to 2,000,000, carboxyvinyl polymers, polyvinyl alcohol, xanthan gum, guar gum, locust bean gum And carboxymethyl cellulose and its derivatives, methyl cellulose and its derivatives, and povidone-polyvinylacetate copolymers.

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