JP6140570B2 - Ibuprofen-containing tablet and method for producing the same - Google Patents

Description

  The present invention relates to an ibuprofen-containing tablet and a method for producing the same.

A tablet containing ibuprofen (ibuprofen-containing tablet) is known as an antipyretic analgesic and the like.
Since ibuprofen is difficult to dissolve in water, it is wet granulated together with excipients such as water-soluble polymers to form granulated particles, and these granulated particles are tableted into ibuprofen-containing tablets. Is common. The ibuprofen-containing tablet obtained by tableting the granulated particles tends to deteriorate the disintegration property. In order to increase the immediate effect such as antipyretic analgesic effect, it is necessary to increase the disintegration property of the tablet. However, simply pursuing the improvement of disintegration property may decrease the hardness of the tablet and become brittle. For this reason, the tablet is required to satisfy both good disintegration property and appropriate hardness.

On the other hand, ibuprofen may cause stomach irritation. For this reason, antacids such as aluminum hydroxide are blended in the ibuprofen-containing tablets in order to suppress the onset of stomach roughness. For example, a pharmaceutical composition containing ibuprofen, etenzamide and aluminum hydroxide has been proposed (for example, Patent Document 1).
However, a preparation in which an acidic component such as ibuprofen and a basic component such as an antacid are blended is likely to cause problems such as discoloration and a decrease in dissolution property due to blending changes.
In order to solve such a problem, a preparation in which an acidic component and a basic component are not directly contacted has been proposed.
For example, a layered preparation has been proposed in which a layer that does not include both is provided between a layer mainly composed of ibuprofen and a layer mainly composed of an antacid (for example, Patent Document 2).
In addition, for example, a granular pharmaceutical in which at least one kind of two or more kinds of granular medicinal components such as an acidic drug and an antacid is coated with a specific coating agent and mixed is proposed (Patent Document 3).
Alternatively, for example, an internal solid preparation containing an antipyretic analgesic component and granulated particles containing an antacid and a specific acid has been proposed (for example, Patent Document 4).

JP 2004-231546 A Japanese Patent Laid-Open No. 05-294829 JP 2006-016329 A JP 2011-068645 A

However, when ibuprofen-containing tablets are produced using conventional techniques, a mixture of each component tends to adhere to a production machine such as a tableting machine. When the mixture adheres to the rotary table of the tableting machine, the rotary table may not rotate and the production work may stop. For this reason, measures such as frequent cleaning of the tableting machine are necessary, and it has been difficult to increase the productivity of ibuprofen-containing tablets.
Therefore, the present invention aims at an ibuprofen-containing tablet having excellent disintegration, moderate hardness, and high productivity.

The ibuprofen-containing tablet of the present invention comprises (A) component: a granulated particle group containing ibuprofen, (B) component: an ungranulated powder of dry aluminum hydroxide gel, and (C) component: an undeveloped silicon dioxide. It contains a mixture with granular powder.
The water content is preferably 2.0% by mass or less.

  The method for producing an ibuprofen-containing tablet of the present invention comprises: (A) component: granulated particle group containing ibuprofen; (B) component: ungranulated powder of dry aluminum hydroxide gel; and (C) component: silicon dioxide. A step of mixing the ungranulated powder with a mixture to obtain a mixture, and a step of tableting the mixture.

  According to the ibuprofen-containing tablet of the present invention, it is excellent in disintegration, has an appropriate hardness, and can improve productivity.

(Ibuprofen-containing tablets)
The ibuprofen-containing tablet of the present invention comprises (A) component: a granulated particle group containing ibuprofen, (B) component: an ungranulated powder of dry aluminum hydroxide gel, and (C) component: an undeveloped silicon dioxide. Contains a mixture with granulated powder.

  The water content of the ibuprofen-containing tablet is preferably 2.0% by mass or less, and preferably 1.6% by mass or less. If it is below the said upper limit, reaction of (A) component and (B) component will be suppressed, and the elution property of ibuprofen will be favorable after storage. The water content of the ibuprofen-containing tablet may be adjusted using a raw material having a low water content, or may be adjusted by being subjected to a drying treatment or the like after being formed into a tablet.

<(A) component: Granulated particle group containing ibuprofen>
Component (A) is a granulated particle group containing ibuprofen (hereinafter sometimes referred to as component (a)). The granulated particles constituting the component (A) are granulated products (ibuprofen-containing particles) containing the component (a). The ibuprofen-containing particles are obtained by granulating the component (a) and an optional component such as an excipient (granulated optional component).
The component (a) is granulated with an excipient or the like to form the component (A), thereby increasing the elution of the poorly water-soluble component (a), and the components (a) and (B) The probability of direct contact is reduced, and the elution of the component (a) can be suppressed from decreasing over time.

(A) 50-500 micrometers is preferable and the average particle diameter of a component has more preferable 100-300 micrometers. If the amount is less than the above lower limit value, powdering may increase and handling may be complicated, and if the value exceeds the upper limit value, the content of the active ingredient in the tablet may be uneven.
The average particle diameter is a volume average particle diameter measured by sieving.

  The content of the component (A) in the ibuprofen-containing tablet is determined in consideration of the dose of the ibuprofen-containing tablet, the content of the component (a) in the component (A), and the like. For example, when the ibuprofen-containing tablet is an OTC medicine, the content of the component (A) in the ibuprofen-containing tablet is an amount capable of ingesting the component (a) of 200 to 600 mg / day.

  (A) Content of (a) component in a component is not specifically limited, For example, 10-99 mass% is preferable and 30-95 mass% is more preferable. If the amount is less than the above lower limit, the content of the component (a) in the component (A) may be too small and the mass per tablet may increase. If the amount exceeds the upper limit, the strength of the ibuprofen-containing particles is low. There is a risk of powdering when tableting.

  The component (A) can contain, as optional components, excipients, binders, disintegrants, drugs (arbitrary drugs) other than the component (a), and the like.

Examples of the excipient include sugars such as lactose and sucrose, sugar alcohols such as mannitol, cellulose such as crystalline cellulose, and inorganic excipients such as calcium silicate. These excipients may be used alone or in combination of two or more.
(A) As for content of the excipient | filler in a component, 0.10-90 mass% is preferable, for example.

Examples of the binder include hydroxypropyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and the like. These binders may be used alone or in a combination of two or more.
(A) As for content of the binder in a component, 1.0-30 mass% is preferable, for example.

Examples of the disintegrant include low-substituted hydroxypropyl cellulose (L-HPC), carmellose, carmellose sodium, carboxymethylcellulose calcium, carboxymethyl starch sodium, croscarmellose sodium, crospovidone, and the like. These disintegrants may be used alone or in combination of two or more.
(A) As for content of the disintegrating agent in a component, 0.30-50 mass% is preferable, for example.

The optional drug is selected according to the use of the ibuprofen-containing tablet, for example, antipyretic analgesic component such as piroxicam, meloxicam, ampiroxicam, celocoxib, rofecoxib, thiaramide, acetaminophen, etenzamide, sulpyrine, loxoprofen sodium; Sedative hypnotic components such as acetylurea and bromvalerylurea; antihistamine components such as diphenhydramine hydrochloride, chlorpheniramine maleate, clemastine fumarate, carbinoxamine maleate; dextromethorphan hydrobromide, dihydrocodine phosphate, codine phosphate , Antitussive ingredients such as tipepidine hibenzate, cloperastine hydrochloride, benzonate; noscapine hydrochloride, bromhexine hydrochloride, potassium guaiacol sulfonate, guaife Expectorant components such as syn; mucosal dissolving components such as L-cysteine hydrochloride, L-methylcysteine hydrochloride and acetylcysteine; mucus repairing components such as carbocysteine; anti-inflammatory enzyme components such as lysozyme chloride; anti-inflammatory components such as glycyrrhizic acid; Mucus lubricating components such as ambroxol; antifungal components such as terbinafine hydrochloride; β2-adrenergic receptor stimulants such as pseudoephedrine, ephedrine hydrochloride, methylephedrine hydrochloride, terbutaline hydrochloride, isoproterenol, salbutamol, terbutaline, theophylline, aminophylline , Xanthine drugs such as proxyphylline, bronchodilating components such as cromoglycic acid or asthma treatment components; amino acids; herbal medicines; fat-soluble vitamins such as vitamins A, D, E, K, U, vitamins B, C, P, etc. Vita, such as water-soluble vitamins Mines etc. are mentioned. These optional drugs may be used singly or in combination of two or more.
The content of the optional drug in the component (A) is appropriately determined in consideration of the content of the optional drug in the tablet optional component described later.

  The moisture content of the component (A) is, for example, preferably 5% by mass or less, preferably 3% by mass or less, and may be 0% by mass. If it is below the said upper limit, (A) component will become difficult to adhere with manufacturing equipment.

The component (A) is produced by a conventionally known granulation method. Examples of the granulation method include a stirring granulation method and a fluidized bed granulation method. Especially, the fluidized-bed granulation method is preferable from the point which can reduce the water content in (A) component.
As the fluidized bed granulation method, for example, the component (a) is mixed with at least one selected from an excipient, a disintegrant and an arbitrary drug, and this is mixed in a granulating apparatus (for example, an air supply temperature of 20). The method of spraying the aqueous solution of binder, making it flow at -70 degreeC) is mentioned.
Another preferable granulation method includes a method of adjusting the water content to an arbitrary amount of water by granulating by a stirring granulation method and then drying by a fluidized bed granulator.

<(B) component: ungranulated powder of dry aluminum hydroxide gel>
The component (B) is an ungranulated powder of dry aluminum hydroxide gel and is not granulated with other components (for example, excipients and the like).

The content of the component (B) in the ibuprofen-containing tablet is determined in consideration of the content of the component (a) in the ibuprofen-containing tablet, but is preferably 1 to 50% by weight, for example, 3 to 30%. % Is more preferable. Moreover, from the point of dosage, 50-1200 mg per daily dose is preferable, and 100-1000 mg is more preferable. If it is more than the said lower limit, the effect by having mix | blended (B) component will be easily exhibited, and if it is below the said upper limit, it will be easy to make content of (A) component and (C) component into an appropriate range.
In the ibuprofen-containing tablet, the mass ratio (B / a ratio) represented by (B) component / (a) component is, for example, preferably 0.20 to 3.0, and more preferably 0.30 to 1.0. . If the B / a ratio is equal to or higher than the above lower limit, the effect of blending the component (B) is easily exhibited, and the mixture can be better prevented from adhering to the manufacturing equipment in the tablet manufacturing method described later. . If the B / a ratio is less than or equal to the above upper limit, discoloration of the component (a) can be easily suppressed.

<(C) component: ungranulated powder of silicon dioxide>
Component (C) is an ungranulated powder of silicon dioxide, and is not granulated with other components (for example, excipients). By using the component (B) and the component (C) in combination, it is possible to better suppress the mixture from adhering to the manufacturing equipment in the tablet manufacturing method described later.

The content of the component (C) in the ibuprofen-containing tablet is, for example, preferably 0.25 to 10% by mass, more preferably 0.5 to 6.0% by mass, and further 1.0 to 4.0% by mass. preferable. If it is more than the said lower limit, the effect by mix | blending (C) component will be easily exhibited, and if it is below the said upper limit, it will be easy to make content of (A) component and (B) component into a suitable range.
In the ibuprofen-containing tablet, the mass ratio (C / a ratio) represented by the component (C) / component (a) is, for example, preferably 0.01 to 0.30, and more preferably 0.04 to 0.25. . If it is above the above lower limit, the effect of blending the component (C) is easily exhibited, and if it is below the above upper limit, the formulation hardness of the ibuprofen-containing tablet is further increased, and the powdering of the mixture described later is improved. Can be suppressed.

The total amount of the component (B) and the component (C) in the ibuprofen-containing tablet is, for example, preferably 3.0 to 60% by mass, and more preferably 5.0 to 25% by mass. If it is at least the above lower limit value, it is possible to better prevent the mixture from adhering to the manufacturing equipment in the production method described later. .
In the ibuprofen-containing tablet, the mass ratio ((B + C) / a ratio) represented by [(B) component + (C) component] / (a) component is preferably 0.10 to 3.0, 0.30 -1.50 is more preferable. If it is at least the above lower limit value, it is possible to better prevent the mixture from adhering to the manufacturing equipment in the production method described later, and if it is not more than the above upper limit value, the content of the component (a) can be easily adjusted to an appropriate range. .

<Optional components of ibuprofen-containing tablets>
The ibuprofen-containing tablet can contain optional components (tablet optional components) other than the components (A) to (C) as long as the effects of the present invention are not impaired. Examples of the tablet optional components include excipients, binders, disintegrants, and drugs (optional drugs) other than the component (a).

Examples of excipients for tablet optional ingredients include corn starch, lactose, talc, crystalline cellulose (Ceolus (trade name, manufactured by Asahi Kasei Chemicals Co., Ltd.)), sugar alcohols such as powdered sugar and mannitol. These excipients may be used alone or in combination of two or more.
The content of the excipient in the ibuprofen-containing tablet (excluding the content of the excipient in the component (A)) is preferably, for example, 0.1 to 90% by mass, and 0.15 to 80% by mass Is more preferable.

Examples of the binder of the tablet optional component include starch, pregelatinized starch, sucrose, gelatin, gum arabic powder, methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, pullulan, dextrin and the like. These binders may be used alone or in a combination of two or more.
The content of the binder in the ibuprofen-containing tablet (excluding the content of the binder in the component (A)) is, for example, preferably 0 to 20% by mass, and more preferably 0.05 to 15% by mass.

Examples of the tablet disintegrating agent include low-substituted hydroxypropylcellulose (L-HPC), carmellose, carmellose sodium, carboxymethylcellulose calcium, carboxymethylstarch sodium, croscarmellose sodium, crospovidone, and the like. These disintegrants may be used alone or in combination of two or more.
The content of the disintegrant in the ibuprofen-containing tablet (excluding the content of the disintegrant in the component (A)) is, for example, preferably 0 to 50% by mass, and more preferably 0.05 to 30% by mass.

As an optional drug as an optional component of the tablet, for example, antipyretic analgesic components such as piroxicam, meloxicam, ampiroxicam, serocoxib, rofecoxib, thiaramide, acetaminophen, etenzamide, sulpyrine, loxoprofen sodium; Hypnotic components: antihistamine components such as diphenhydramine hydrochloride, chlorpheniramine maleate, clemastine fumarate, carbinoxamine maleate; dextromethorphan hydrobromide, dihydrocodine phosphate, codine phosphate, tipepidine hibenzate, cloperastine hydrochloride, Antitussive components such as benzonate; expectorant components such as noscapine hydrochloride, bromhexine hydrochloride, potassium guaiacol sulfonate, and guaifenesin; L-system hydrochloride Mucosal dissolving components such as chlorocysteine, L-methylcysteine and acetylcysteine; mucus repairing components such as carbocysteine; anti-inflammatory enzyme components such as lysozyme chloride; anti-inflammatory components such as glycyrrhizic acid; mucus lubricating components such as ambroxol hydrochloride; Antifungal ingredients such as terbinafine hydrochloride; pseudoephedrine, ephedrine hydrochloride, methylephedrine hydrochloride, terbutaline hydrochloride, isoproterenol, salbutamol, β2-adrenergic receptor stimulants such as terbutaline, xanthine drugs such as theophylline, aminophylline, proxyphylline, Bronchodilating components such as cromoglycic acid or asthma treatment components; amino acids; herbal medicines; fat-soluble vitamins such as vitamins A, D, E, K, U, vitamins such as water-soluble vitamins such as vitamins B, C, P, etc. Is mentioned. These optional drugs may be used singly or in combination of two or more.
The content of the optional drug in the ibuprofen-containing tablet (excluding the content of the optional drug in the component (A)) is appropriately determined in consideration of the content of the optional drug in the component (A).

(Method for producing ibuprofen-containing tablets)
The manufacturing method of the ibuprofen containing tablet of this invention is equipped with the process (mixing process) of mixing a component (A)-(C) and obtaining a mixture, and the process of compressing a mixture (molding process).

The mixing step is a step of obtaining a powder mixture by powder-mixing the components (A) to (C).
The mixing method is not particularly limited, and examples thereof include a method of mixing each component using a conventionally known powder mixer.

  The blending amount of the component (A) in the mixing step is determined in consideration of the dose of the ibuprofen-containing tablet, the content of the component (a) in the component (A), and the like.

The blending amount of the component (B) in the mixing step is determined in consideration of the content of the component (a) in the component (A), the blending amount of the component (A), and the like. -50 mass% is preferable and 3-30 mass% is more preferable. If it is more than the said lower limit, it can prevent more favorably that a mixture adheres to a manufacturing apparatus. If it is below the said upper limit, it will be easy to make content of (A) component and (C) component into a suitable range.
In the mixture, the mass ratio (B / a ratio) represented by (B) component / (a) component is, for example, preferably 0.20 to 3.0, and more preferably 0.30 to 1.0. If B / a ratio is more than the said lower limit, the effect by having mix | blended (B) component will become easy to be exhibited, and it can prevent more favorably that a mixture adheres to a manufacturing apparatus. If the B / a ratio is less than or equal to the above upper limit, discoloration of the component (a) can be easily suppressed.

The blending amount of the component (C) in the mixing step is determined in consideration of the content of the component (a) in the component (A), the blending amounts of the components (A) to (B), and the like. In the mass%, 0.25 to 10 mass% is preferable, 0.5 to 6.0 mass% is more preferable, and 1.0 to 4.0 mass% is more preferable. If it is more than the said lower limit, the effect by mix | blending (C) component will be easy to be exhibited, and it can prevent more favorably that a mixture adheres to a manufacturing apparatus. If it is below the said upper limit, it will be easy to make content of (A) component and (B) component into an appropriate range.
In the mixture, the mass ratio (C / a ratio) represented by the component (C) / component (a) is, for example, preferably 0.01 to 0.30, and more preferably 0.04 to 0.25. If it is more than the said lower limit, the effect by mix | blending (C) component will become easy to be exhibited, and it can prevent more favorably that a mixture adheres to a manufacturing apparatus. If it is below the said upper limit, content of (a) component can be made into an appropriate range, the formulation hardness of an ibuprofen containing tablet can be raised more, and the powdering of a mixture can be suppressed favorably.

In the mixing step, the total amount of the component (B) and the component (C) in the mixture is preferably, for example, 3.0 to 60% by mass, and more preferably 5.0 to 25% by mass. If it is more than the said lower limit, it can prevent better that a mixture adheres to a manufacturing apparatus, and if it is below the said upper limit, it will be easy to make content of (A) component into an appropriate range.
In the mixture, the mass ratio ((B + C) / a ratio) represented by [(B) component + (C) component] / (a) component is preferably 0.10 to 3.0, preferably 0.30 to 1 .50 is more preferred. If it is at least the above lower limit value, it is possible to better prevent the mixture from adhering to the manufacturing equipment in the production method described later, and if it is not more than the above upper limit value, the content of the component (a) can be easily adjusted to an appropriate range. .

  The mixing order is not particularly limited, and for example, all the components may be charged into a mixer and mixed, or each component may be sequentially added to the mixer and mixed.

  The mixing time is not particularly limited, and is a time during which each component can be dispersed approximately uniformly.

  Although the water content of a mixture is not specifically limited, For example, 10 mass% or less is preferable and 5 mass% or less is more preferable. If it is below the said upper limit, drying efficiency will be improved and (A) component will become difficult to adhere with manufacturing equipment.

The molding step is a step of tableting the mixture obtained in the mixing step to obtain tablets of any shape. In the molding step, since the mixture contains the components (A) to (C), it is difficult to adhere to a tableting machine (particularly a rotating disk). For this reason, an ibuprofen containing tablet can be manufactured with high productivity.
The tableting method is not particularly limited, and includes a method using a conventionally known tableting machine.
The tableting conditions are not particularly limited, and are appropriately determined in consideration of the hardness (tablet hardness) required for ibuprofen-containing tablets.

After the molding step, the ibuprofen-containing tablet may be coated as necessary (coating step).
The coating treatment is not particularly limited, and a conventionally known method can be applied. Examples thereof include a method of applying a coating agent such as an aqueous solution of a polymer, a plasticizer or the like to the surface and then drying.

  As described above, since the ibuprofen-containing tablet of the present invention contains a mixture of the components (A) to (C), the tablet is excellent in disintegration and handling properties, and the mixture is difficult to adhere to manufacturing equipment, so that productivity is improved. Excellent.

  EXAMPLES Hereinafter, although an Example is shown and this invention is demonstrated in detail, this invention is not limited by the following description.

(Raw materials used)
The raw materials used in Examples and Comparative Examples are as shown in Table 1.

Production Example 1 Production of Component (A) 1500 g of ibuprofen and 600 g of low-substituted hydroxypropylcellulose (LH-31) were mixed in a polyethylene bag. This was put into a fine pulverizer Coroplex (manufactured by Paulec Co., Ltd., 160Z type), and pulverized under the condition of a rotational speed of 14,000 rpm. 1610 g of the obtained pulverized product was put into a pre-heated Spiraflow SFC-5 type (manufactured by Freund Sangyo Co., Ltd.), under the conditions of an intake air temperature of 60 ° C., an exhaust air volume of 2.7 m ³ / min, and a rotor rotational speed of 200 rpm. Fluidized. After confirming that the exhaust temperature is 43 ° C. or higher, using a two-fluid nozzle ATF type (hole diameter φ1.8 mm), an aqueous solution of a binding liquid (hydroxypropylcellulose: purified water = 389.3: 6099 (mass basis) ) At a liquid speed of 100 mL / min. The liquid speed was changed to 60 mL / min 10 minutes after the start of spraying. The total amount of binding solution sprayed was 2415 g. After spraying, the drying operation was started. When the exhaust temperature reached 43 ° C., the drying operation was finished to obtain a granulated product. The obtained granulated material was sieved in whole using a sieve having an aperture of 600 μm (sieving while sieving the sieved product with a spatula) to obtain component (A).

(Examples 1-9, Comparative Examples 1-2)
Each component was mixed in a polyethylene bag so as to have the composition shown in Table 2 to obtain a mixture (mixing step). The mass (mg) described in Table 2 is the total mass of one ibuprofen-containing tablet.
Using a rotary tableting machine (LIBRA2 manufactured by Kikusui Seisakusho Co., Ltd.), the obtained mixture was continuously tableted under the following tableting conditions to obtain tablets (molding step). Under the present circumstances, the adhesion prevention effect mentioned later was evaluated.
The rotary tableting machine used was equipped with a φ9.0 mm (two-stage R) punch and mortar.
In addition, (B ') component is the granulated particle group which granulated dry aluminum hydroxide gel, the low substituted hydroxypropyl cellulose, and the hydroxypropyl cellulose according to the composition in a table | surface.

<Tabletting conditions>
The number of rotations of the rotating disk: 30 rpm.
The rotation speed of the stirring feed shoe: 100 rpm.
Preload: 1 kN.
Main pressure: 8 kN.

The obtained tablet was coated by the following method using Aqua Coater Model 48.
First, a coating agent was prepared by dispersing and dissolving the coating agent in water. The coating liquid is sprayed onto the tablets under the conditions of a supply air temperature of 60 ° C., a supply air flow of 2.3 m ³ / min, and an exhaust temperature of 42 ± 2 ° C., and then a supply air temperature of 60 ° C. and a supply air flow of 2.3 m ³ / Min for 90 minutes to obtain ibuprofen-containing tablets of each example.
About the obtained ibuprofen containing tablet, disintegration time and tablet hardness were evaluated, and the result is shown in the table.

(Evaluation method)
<Adhesion prevention effect>
The molding process was continuously performed, and the adhesion state of the powder on the rotating disk was visually observed, and the adhesion preventing effect was evaluated according to the following evaluation criteria.

≪Evaluation criteria≫
A: In the molding process for 60 minutes, adhesion of powder to the rotating disk was not recognized.
A: Adhesion of powder to the rotating disk was observed in the molding process for 30 to 60 minutes.
X: Adhesion of the powder to the rotating disk was recognized in the molding process of less than 30 minutes.

<Collapse time>
The 6 ibuprofen-containing tablets in each case were measured for disintegration time using water in accordance with the disintegration test method of the Japanese Pharmacopoeia (16th revision). The average value of the test results of 6 tablets was obtained, and the obtained average value was classified into the following evaluation criteria.

≪Evaluation criteria≫
A: Collapse time is less than 1 minute.
○: Disintegration time is 1 minute or more and less than 5 minutes.
X: Collapse time is 5 minutes or more.

<Tablet hardness>
The hardness of 10 ibuprofen-containing tablets in each example was measured with a hardness meter (Pharma Test Corp., Type PTB301 type). The average value of the test results of 10 tablets was obtained, and the obtained average value was classified into the following evaluation criteria.

≪Evaluation criteria≫
A: Hardness 10.0 kgf or more.
○: Hardness of 7.0 kgf or more and less than 10.0 kgf.
X: Hardness less than 7.0 kgf.

As shown in Table 2, in Examples 1 to 9 to which the present invention was applied, the adhesion preventing effect, the disintegration time, and the tablet hardness were “◎” or “◯”.
In Comparative Example 1 containing no component (C), the adhesion preventing effect was “x”. In Comparative Example 2 containing the component (B ′) instead of the component (B), the adhesion preventing effect and the tablet hardness were “x”.

(Example 10)
An ibuprofen-containing tablet was obtained in the same manner as in Example 1 except that no coating was applied so as to obtain the composition shown in Table 3. The mass (mg) described in Table 3 is the total mass of one ibuprofen-containing tablet. About the obtained ibuprofen containing tablet, the maintenance factor of dissolution property was calculated | required and the result is shown in a table | surface.

(Example 11)
(B) Ibuprofen was carried out in the same manner as in Example 10 except that the component was placed in a dryer (DN-93 type, manufactured by Yamato Scientific Co., Ltd.), subjected to a drying process at 105 ° C. for 2 hours and then subjected to a mixing step. A containing tablet was obtained. About the obtained ibuprofen containing tablet, the maintenance factor of dissolution property was calculated | required and the result is shown in a table | surface.

(Example 12)
The tablet of Example 11 was placed in a thermostatic bath (VACUUM DRYING OVEN SVD10) and dried for 4 hours and 30 minutes. The drying conditions were a pressure of 0.09 MPa and 45 ° C. About the obtained ibuprofen containing tablet, the maintenance factor of dissolution property was calculated | required and the result is shown in a table | surface.

(Evaluation method)
<Moisture content>
After pulverizing 15 ibuprofen-containing tablets of each example with a mortar, the mass change rate (mass%) was measured (60 ° C., 20 minutes) with an electronic moisture meter (manufactured by Shimadzu Corporation, MOC-120H). The obtained mass change rate was defined as the water content of the ibuprofen-containing tablet.

<Elution maintenance ratio>
Each ibuprofen-containing tablet was sealed in a bottle and stored at 50 ° C. for 6 weeks. In accordance with the dissolution test method of the Japanese Pharmacopoeia (16th revision), an initial dissolution product and a tablet after storage are subjected to a dissolution test using 900 mL of pH 4.5 (USP) test solution, and (a ) The elution amount of the component (ibuprofen) was measured. The dissolution retention rate was calculated as a percentage by dividing the dissolution amount of the tablet after storage by the dissolution amount of the initial product. It can be said that the higher the maintenance rate, the less the degradation of dissolution during storage.

  As shown in Table 3, Examples 1, 10, 11, and 12 having a water content of 2.0% by mass or less had a high elution maintenance rate.

Claims (5)

(A) Component: Contains a mixture of granulated particles containing ibuprofen, (B) component: ungranulated powder of dry aluminum hydroxide gel, and (C) component: ungranulated powder of silicon dioxide. An ibuprofen-containing tablet, wherein the component (B) has a water content of 10% by mass or less, and the ibuprofen-containing tablet has a water content of 1.8% by mass or less . The ibuprofen-containing tablet according to claim 1, wherein the content of ibuprofen in the component (A) is 10 to 99% by mass. The ibuprofen-containing tablet according to claim 1 or 2, wherein a mass ratio represented by [(B) component + (C) component] / ibuprofen is 0.10 to 3.0. (A) component: granulated particle group containing ibuprofen, (B) component: ungranulated powder of dry aluminum hydroxide gel, and (C) component: ungranulated powder of silicon dioxide And obtaining
The tableting method of the said mixture is provided, The manufacturing method of the ibuprofen containing tablet as described in any one of Claims 1-3 characterized by the above-mentioned. The manufacturing method of the ibuprofen containing tablet of Claim 4 further equipped with the process of giving a drying process to the said (B) component before the process of obtaining the said mixture.