KR100253525B1 - Ibuprofen-containing solid composition - Google Patents

Abstract

The present invention discloses a coated ibuprofen-containing solid composition composed of a sugar alcohol or saccharide coated on a surface of the ibuprofen-containing core and the surface of the ibuprofen-containing core with a water-insoluble high molecular compound. The composition of the present invention masks the irritating bitter taste of ibuprofen in ibuprofen containing solid preparations. In addition, these solid preparations suppress the irritating bitter taste and sublimation of ibuprofen and have a continuous masking effect, and exhibit excellent stability over time, with no particles being hygroscopic, solidified or discolored.

Description

Ibuprofen-containing solid composition

The present invention relates to a ibuprofen-containing solid composition which suppresses the irritating bitter taste of ibuprofen and is stable over time, and a method for producing the same.

Ibuprofen, 2- (4-isobutylphenyl) propionic acid, has anti-inflammatory, antipyretic and analgesic properties and is widely used as a medicament. However, there are various problems with the preparation of oral ibuprofen-containing drugs.

That is, one of these problems is a method of suppressing the irritating bitter taste of ibuprofen. Due to this bitter taste, most ibuprofen drugs are in the form of capsules or tablets (film coated tablets, dragees). There are few granules or granules of ibuprofen, such as microgranules and powders.

In order to reduce the bitter taste of ibuprofen in granules, a method of adding aluminum hydroxide (Japanese Patent Laid-Open No. 10321/1988), a method of preparing granules or microgranules by kneading ibuprofen with a gastric high molecular compound, and the like have been proposed. However, the effectiveness of these methods is not yet sufficient.

Another problem with ibuprofen containing medicaments relates to the low melting point (75-77 ° C.) of ibuprofen. Ibuprofen sublimates over time, reducing the masking effect and causing changes such as wetting, solidification and discoloration. In particular, when the ibuprofen formulation contains components that adversely affect ibuprofen or are adversely affected by ibuprofen, separation of granules that prevent such changes may not have a sufficient effect. In order to prevent moisture absorption or solidification over time, addition of commonly used solidification agents such as hard silicic anhydride (Adosolder 101, Aerosil 200, etc.) and talc has little effect on the absorption and solidification of ibuprofen-containing solid preparations.

Thus, there was no solution to effectively overcome the above problems in ibuprofen-containing solid formulations. Granules such as granules, microgranules and powders are widely used in conventional medicines or pharmaceuticals because of their advantages such as good compatibility with other powders and ease of taking. However, ibuprofen was inconvenient to apply to such formulations.

In addition to these benefits, powders can be made from other preparations, such as capsules or tablets. This is another reason for the need for ibuprofen-containing solid preparations.

Accordingly, it is an object of the present invention to provide an ibuprofen-containing solid formulation that is easy to inhibit and take on the irritating bitter taste of ibuprofen and is stable over time.

The present inventors earnestly studied in order to achieve this object, and as a result, the ibuprofen-containing solid preparation obtained by coating a core containing ibuprofen as an active ingredient with a water-insoluble polymer compound and forming a sugar alcohol or saccharide layer on the surface thereof is ibuprofen. It has been found to suppress the irritating bitter taste and sublimation, and have a lasting masking effect. It has also been found that this formulation is stable without causing any changes such as moisture absorption, solidification and discoloration over time.

In addition, the inventors have found that such ibuprofen-containing solid preparations can be usefully used as capsules or raw materials for purification.

That is, the first object of the present invention is composed of ibuprofen-containing particles, a water-insoluble high molecular compound and a sugar alcohol or saccharide, and the surface of the ibuprofen-containing particles is coated with a water-insoluble high molecular compound, the surface of the sugar alcohol or saccha It is to provide a ibuprofen-containing solid composition coated with a ride.

A second object of the present invention is to provide a method for producing a ibuprofen-containing solid composition characterized by coating the ibuprofen-containing particles with a water-insoluble high-molecular compound, and coating the coating surface of the water-insoluble high-molecular compound compound with sugar alcohol or saccharide. It is.

Hereinafter, the present invention will be described in detail.

In order to prepare the ibuprofen-containing solid composition of the present invention, the surface of the ibuprofen-containing particles is first coated with a water-insoluble high molecular compound.

There is no particular limitation on the method for producing ibuprofen-containing particles having a composition of the present invention as a core. Assembly methods commonly used in the assembly method, such as stirring granulation, fluidized bed granulation, dry granulation using a roll granulator, extrusion granulation and the like can be used. Of these, extrusion granulation that provides a narrow particle size distribution is particularly preferred. The particle size may be in any range as long as it is in the range of ordinary granules, microgranules and powders, and is preferably in the range of 30 to 42 mesh.

The water-insoluble high molecular compound coating the particles is not particularly limited as long as it is a compound commonly used in pharmaceutical preparations. Preferred are ethyl cellulose and acrylic type polymers. Especially preferred commercially available products include aqueous dispersions of ethyl cellulose such as Aquacoat (trade name; manufactured by Asahi Chemical Industries), Surelease (trade name; manufactured by Nippon Calacone); Aqueous dispersions of aminoalkyl methacrylate copolymers such as Eudragit RS30D (trade name; manufactured by Rohm Pharma); And an aqueous dispersion of methyl methacrylate-ethyl acrylate such as Oiradgit NE30D (trade name; manufactured by Rohm Pharma).

The amount of the water-insoluble high molecular compound coated on the particles is 2 to 10% by weight (hereinafter referred to simply as "%"), preferably 3 to 5%, based on the ibuprofen-containing core particles. The coating can be carried out using conventional fluid bed granulators, roll fluid bed granulators or centrifugal roll granulators.

Ibuprofen-containing particles whose surfaces are coated with a water-insoluble high molecular compound are again coated with sugar alcohol or saccharide to form a coating layer.

Examples of sugar alcohols or saccharides include D-mannitol, xylitol, sorbitol, refined sugar, lactose, glucose, reduced maltose and the like.

The amount of these sugar alcohols or saccharides to be coated is 2 to 20%, preferably 5 to 10% with respect to the core ibuprofen-containing particles. This coating can be carried out by conventional methods using a fluidized bed granulator, a rolled fluidized bed granulator or a centrifugal roll granulator.

The coating of the water-insoluble polymer compound may optionally contain a hydrophobic material such as talc or a plasticizer such as glycerol fatty acid ester, and the coating of sugar alcohol or saccharide may contain fragrances, pigments, sweeteners, etc. which are commonly used in medicine. good.

The ibuprofen-containing solid preparation thus prepared may be used as a powder such as microgranules or granules as it is. In addition, it is possible to fill this into a different type of solid preparation, that is, a capsule, to make a capsule, or to make an tablet by extrusion molding.

The irritating bitter taste of ibuprofen in the ibuprofen-containing solid preparations of the present invention is masked. In addition, such solid preparations are easy to administer because they do not impart a rough feeling to the coating agent. Moreover, its handling is simple because of its electrostatic properties. Moreover, since it has the ability to suppress sublimation of ibuprofen over a long time, the particles are prevented from being absorbed, solidified or discolored, and exhibits excellent stability over time. Drugs that affect ibuprofen properties such as ascorbic acid, maleic acid chlorophenylamine or methylefedoline hydrochloride are particularly effective when combined together.

Hereinafter, although an Example is given and this invention is demonstrated concretely, this invention is not limited to these Examples.

Example 1

(1) 1,800 g of ibuprofen, 2,240 g per tablet, crystalline cellulose ("AVICEL PH01", trade name, manufactured by Asahi Chemical Industries) 288 g, corn starch 320 g, and hydroxypropyl cellulose (HPC-L, trade name, manufactured by Nippon Soda) 112 g Was mixed in a vertical granulator FM-VG-25 (trade name, manufactured by Paulec). 500 g of purified water containing 40 g of polyoxyl 40 stearate (MYS-40) was added, followed by kneading, followed by kneading, and a twin-domlan TDG-110 type granulator (trade name, manufactured by Fuji, Powdal, screen diameter; 0.4 mm). , Thickness: 0.4mm). The granules were dried in a fluidized Glat WSG-5 (trade name, manufactured by Ohkawara Co., Ltd.) and struck with 30 and 42 mesh sieves to obtain extruded ibuprofen-containing particles having a particle size of 30 to 42 mesh.

(2) The obtained particles were coated with the material of the following composition using flow type Glat WSG-5 such that the amount of aquacoat was 5% of the particles.

Next, a 20% aqueous solution of D-mannitol was sprayed onto the particles obtained so that the amount of D-mannitol was 5% of the particles, and the particles were dried to obtain a ibuprofen-containing granule.

Example 2

Ibuprofen-containing particles were prepared in the same manner as in Example (1), and the coating material of the following composition was coated using the flow type Glat WSG-5 in an amount such that the amount of the eudragit NE30D was 3% of the particles.

Then, a 20% aqueous solution of D-mannitol was sprayed onto the obtained particles so that the amount of D-mannitol was 5% of the particles, and the particles were dried to obtain an ibuprofen-containing granule.

Example 3

Ibuprofen-containing particles were prepared in the same manner as in Example (1), and the coating material of the following composition was coated using a flow type Glat WSG-5 such that the amount of Oidragit RS30D was 5% of the particles.

Thereafter, a 20% aqueous solution of lactose was sprayed onto the obtained particles so that the amount of lactose was 5% of the particles, and the particles were dried to obtain ibuprofen-containing granules.

Example 4

Ibuprofen-containing particles were prepared in the same manner as in Example (1), and the coating material of the following composition was prepared using a flow type Glat WSG-5 such that the amount of Surrelease (Surelease, manufactured by Nippon Calacone) was 5% of the particles. Covered.

Then, even if the amount of D-mannitol was 5% of the particles, a 20% aqueous solution of D-mannitol was sprayed onto the particles obtained above, and the particles were dried to obtain an ibuprofen-containing granule.

Example 5

Ibuprofen-containing particles were prepared in the same manner as in Example (1), and the coating material of the following composition was coated using a flow type Glat WSG-5 such that the amount of ethyl cellulose was 5% of the particles.

Thereafter, a 20% aqueous solution per tablet bag was sprayed onto the particles obtained above so that the amount of tablet bags was 10% of the particles, and the particles were dried to obtain an ibuprofen-containing granule.

Comparative Example 1

Ibuprofen-containing particles were prepared in the same manner as in Example (1), and the coating material of the following composition was flow-type Glat WSG- such that the amount of polyvinylacetal diethylaminoacetate and hydroxypropyl cellulose was 5% of the particles, respectively. Covered using 5.

Comparative Example 2

Ibuprofen-containing particles were prepared in the same manner as in Example (1), and were coated using the flowable Glat WSG-5 coating material having the following composition so that the amount of "aqua coat" was 5% of the particles.

Comparative Example 3

To the particles of Comparative Example 2 were added Adosolider 101 (0.2%) and talc (0.5%).

[Comparative Example 4]

Ibuprofen-containing particles were prepared in the same manner as in Example (1), and the coating material of the following composition was coated using the flow type Glat WSG-5 such that the amount of "aqua coat" was 5% of the particles.

Then, the ethanol solution of 5% hydroxypropyl cellulose was sprayed onto the particles obtained above so that the amount of hydroxypropyl cellulose (HPC-SL) was 10% of the particles, and the particles were dried Ibuprofen-containing granules were obtained.

[Test Example 1]

The granules obtained in Examples 1 to 5 and Comparative Examples 1 to 4 were heat-sealed with aluminum and stored in a thermostat at 50 ° C. for one month, and then tested for hygroscopic / solidification and discoloration of the specimens. The results are shown in Table 1.

TABLE 1

The granules prepared in Examples 1 to 5 do not cause moisture absorption and solidification during preparation and after storage, and exhibit an excellent masking effect and do not cause discoloration after storage. On the contrary, the products of Comparative Examples 1 to 4, that is, granules coated with a mixture of a gastric polymer compound and a water-soluble polymer compound (Comparative Example 1), granules coated with only a water-insoluble polymer compound (Comparative Example 2), adosolger 101 and The granulating agent (Comparative Example 3) to which the anti-solidifying agent such as talc was added and the granulating agent (Comparative Example 4) coated with the water-insoluble high molecular compound and forming the water-soluble high molecular compound layer all decreased the masking effect over time. Causes solidification and discoloration.

Example 6

30 g of maleic acid chlorophenylamine, 300 g of anhydrous caffeine, 3,762 g of lactose, 288 g of low-substituted hydroxypropyl cellulose, 288 g of corn starch and hydroxypropyl cellulose in a vertical granulator "FM-VG-25" (brand name, product made by Pawlec) 60 g of oze was added and mixed. 900 g of purified water containing 40 g of polyoxyl 40 stearate (MYS-40) was added, followed by kneading and granulation with a twin-domlan TDG-100 granulator (screen diameter: 0.4 mm Φ, thickness: 0.4 mm). The obtained granules were dried in a fluidized Glat WSG-5, and sieved into 30 and 40 mesh bodies to obtain extruded ibuprofen-containing particles (A) having a particle size of 30 to 42 mesh. This particle | grain (A) was mixed with the ibuprofen containing particle | grains manufactured in Example 1, and the mixed particle was obtained.

Example 7

1,200 g of ascorbic acid, 2,732 g per tablet bag, 288 g of low-substituted hydroxypropyl cellulose, 288 g of corn starch, and 60 g of hydroxy propyl cellulose were mixed in a vertical granulator "FM-VG-25" (trade name, manufactured by Pawlec). It was. 300 g of purified water containing 40 g of polyoxyl 40 stearate (MYS-40) was added and kneaded, followed by twin dome gran TDG-100 granulator (screen particle diameter: 0.4 mm). , Thickness: 0.4mm). The obtained granules were dried in a flowing Glat WSG-5, and sieved into 30 and 42 mesh bodies to obtain extruded ibuprofen-containing particles (B) having a particle size of 30 to 42 mesh. This particle | grain (B) was mixed with the ibuprofen containing particle | grains manufactured in Example 1, and the mixed particle was obtained.

Example 8

Ibuprofen-containing particles (A) and (B) prepared in Examples 6 and 7 were mixed with the ibuprofen-containing particles prepared in Example 1.

[Comparative Example 5]

Ibuprofen-containing particles (A) prepared in Example 6 were mixed with ibuprofen-containing particles obtained in Comparative Example 3 to obtain mixed particles.

Comparative Example 6

Ibuprofen-containing particles (B) prepared in Example 7 were mixed with ibuprofen-containing particles obtained in Comparative Example 3 to obtain mixed particles.

Comparative Example 7

Ibuprofen-containing particles (A) and (B) prepared in Examples 6 and 7 were mixed with the ibuprofen-containing particles obtained in Comparative Example 1 to obtain mixed particles.

[Test Example 2]

The mixed particles obtained in Examples 6 to 8 and Comparative Examples 5 to 7 were heat-sealed with aluminum and stored in a constant temperature bath at 50 ° C. for one month, and then the hygroscopic / solidification and discoloration of the specimens were tested. The results are shown in Table 2.

TABLE 2

In the particles of Examples 6 to 8, there was no moisture absorption, solidification and discoloration, but all of the particles of Comparative Examples 5 to 7 caused moisture absorption, solidification and discoloration.

Example 9

1,320 g of ibuprofen-containing particles prepared in Example 1, 780 g of crystalline lactose (80M: trade name, manufactured by Die Melkindustrie Veghel), 100 g of croscarmellose sodium (Ac-Di-Sol: trade name, manufactured by Asahi Chemical Industries), talc 25 g and 25 g of magnesium stearate were mixed in a V-type mixer (V-10: trade name, manufactured by Tokuju Kosakusho Co.), tableted using a single tablet press (N-30E: manufactured by Okada Seisakusho Co.), and weighed 250 mg by weight and 3.4 mm thick. And tablets having a diameter of 9 mm were obtained.

Example 10

2,640 g of ibuprofen-containing particles and 60 g of hard silicic anhydride prepared in Example 1 were mixed in a V-type mixer (V-10: trade name, manufactured by Tokuju Kosakusho Co.) and placed in capsule No. 1 using a capsule filling machine. Each capsule contains 450 mg of this mixture.

Claims (6)

An ibuprofen-containing solid composition comprising ibuprofen-containing particles, a water-insoluble high molecular compound and a sugar alcohol or a saccharide, coated with a water-insoluble high molecular compound on the surface of the ibuprofen-containing particle, and coated with a sugar alcohol or a saccharide on the coating surface. The ibuprofen-containing solid composition according to claim 1, wherein the amount of the water-insoluble high molecular compound coated on the particles is 2 to 10% by weight based on the ibuprofen-containing particles. The ibuprofen-containing solid composition according to claim 1, wherein the amount of sugar alcohol or saccharide to be coated is 2 to 20% by weight based on the ibuprofen-containing particles. The ibuprofen-containing solid composition according to claim 1, which is a fine granule, granule, capsule or tablet. A method for producing a ibuprofen-containing solid composition, wherein the ibuprofen-containing particles are coated with a water-insoluble high molecular compound, and the coating surface is coated with a sugar alcohol or a saccharide. A pharmaceutical composition comprising a ibuprofen-containing solid composition as defined in claim 1 and a solid composition containing a drug selected from the group consisting of ascorbic acid, maleic acid chlorophenylamine, and methylephedolin hydrochloride.