JP2021066742A - Laminated tablets - Google Patents

Abstract

To provide laminated tablets that are less likely to cause delamination, in laminated tablets manufactured by a manufacturing method comprising a precompression step.SOLUTION: Provided is a laminated tablet 1 with an approximately columnar shape that comprises a first layer 10 and a second layer 20 adjacent to the first layer 10 at the boundary surface, both or either one of the first layer 10 and the second layer 20 containing at least one component (α) selected from the following components (A) and (B): component (A) at least one selected from a dry aluminum hydroxide gel, aluminum glycinate, magnesium carbonate, magnesium oxide, magnesium aluminate metasilicate, synthetic hydrotalcite, glycine, and sucralfate; and component (B) at least one selected from loxoprofen and a salt thereof.SELECTED DRAWING: Figure 1

Description

The present invention relates to laminated tablets.

As a method for producing a tablet having a plurality of layers (laminated tablet), there is a method including a so-called precompression step. In the manufacturing method including a pre-compression step, the powder constituting the lower layer is compressed at an arbitrary pressure (pre-compression step), and the powder constituting the upper layer is placed on the powder that has undergone the pre-compression step to form the lower layer. This is a method of forming a lower layer and an upper layer by compressing the powder to be formed and the powder constituting the upper layer at a pressure higher than that in the precompression step (this compression step). By providing the pre-compression step, the obtained laminated tablet has a clear boundary between the upper layer and the lower layer. In addition, by providing the precompression step, the density of the obtained laminated tablet can be increased and the size of the laminated tablet can be reduced. Further, by providing the pre-compression step, the contact area between the components of each layer in the obtained laminated tablet can be reduced, and the change of the components of each layer can be suppressed.

Laminated tablets produced by a production method including a precompression step have a problem that they are easily peeled off at the interface between the upper layer and the lower layer.
To solve such a problem, a laminated tablet having a concave engraving on the surface has been proposed (for example, Patent Document 1). According to the invention of Patent Document 1, peeling (delamination) between adjacent layers is suppressed.

International Publication No. 2012/118180

However, in the invention of Patent Document 1, since a punch having a convex portion having a shape corresponding to the concave marking is used, the powder constituting the upper layer tends to adhere to the punch, and the marking tends to be unclear. Further, in the invention of Patent Document 1, the engraved portion is easily scraped during storage, and the engraved portion tends to be unclear when the coating layer is provided on the surface. In addition, since the invention of Patent Document 1 requires marking on the surface, there are restrictions on the appearance.
Therefore, the present invention aims at a laminated tablet produced by a manufacturing method including a precompression step, in which delamination is less likely to occur.

As a result of diligent studies, the present inventors have found that delamination can be satisfactorily suppressed by blending a specific component in at least one of adjacent layers.

That is, the laminated tablet of the present invention is a substantially columnar laminated tablet having a first layer and a second layer adjacent to the first layer at a boundary surface, and the first layer and the laminated tablet Both or one of the second layers is characterized by containing at least one (α) component selected from the following component (A) and the following component (B).
(A) Ingredient: At least one selected from dry aluminum hydroxide gel, aluminum glycinate, magnesium carbonate, magnesium oxide, magnesium aluminometasilicate, synthetic hydrotalcite, glycine and sucralfate.
(B) Ingredient: At least one selected from loxoprofen and its salt.
The surface of the second layer opposite to the boundary surface preferably has the same shape as the boundary surface, and the surface of the second layer opposite to the boundary surface and the boundary surface Is preferably a curved surface that bulges in the same direction, preferably has a diameter of 6 to 13 mm in a plan view, and preferably has a height of 3 to 10 mm, and is a layer containing the component (α). The water content of the above is preferably 2 to 13% by mass.

The method for producing a laminated tablet of the present invention includes a first layer, a second layer adjacent to the first layer, and / or one of the first layer and the second layer. , A method for producing a laminated tablet containing at least one component (α) selected from the following component (A) and the following component (B), wherein the first powder constituting the first layer is optional. The second powder constituting the second layer is placed on the first compression step of compressing with the pressure of the above and the first powder that has undergone the first compression step, and the first compression is performed. The present invention includes a second compression step of compressing the first powder and the second powder at a pressure higher than that of the step to form the first layer and the second layer. It is characterized by.
(A) Ingredient: At least one selected from dry aluminum hydroxide gel, aluminum glycinate, magnesium carbonate, magnesium oxide, magnesium aluminometasilicate, synthetic hydrotalcite, glycine and sucralfate.
(B) Ingredient: At least one selected from loxoprofen and its salt.
It is preferable to provide an intermediate compression step between the first compression step and the second compression step, and the pressure in the intermediate compression step is preferably 1 to 4 kN, and the pressure in the first compression step. Is 1 to 3 kN, and the pressure in the second compression step is preferably more than 3 kN.

The laminated tablet of another aspect of the present invention comprises a first layer and a second layer adjacent to the first layer, and the first powder constituting the first layer has an arbitrary pressure. The second powder constituting the second layer is placed on the first powder compressed with, and then compressed at an arbitrary pressure, at a pressure higher than the pressure with respect to the first powder. A laminated tablet obtained by compressing the first powder and the second powder to form the first layer and the second layer, wherein the first layer and the second layer are formed. Both or one of the two layers is characterized by containing at least one (α) component selected from the following component (A) and the following component (B).
(A) Ingredient: At least one selected from dry aluminum hydroxide gel, aluminum glycinate, magnesium carbonate, magnesium oxide, magnesium aluminometasilicate, synthetic hydrotalcite, glycine and sucralfate.
(B) Ingredient: At least one selected from loxoprofen and its salt.
The first layer contains the (α) component, and the content of the (α) component in the first layer is preferably 10 to 80% by mass, and the water content of the first layer is high. The amount is preferably 2 to 13% by mass.
The second layer contains the component (α), and the content of the component (α) in the second layer is preferably 10 to 80% by mass, and the water content of the second layer is high. The amount is preferably 2 to 13% by mass.

The laminated tablet of the present invention is less likely to cause delamination.

(A) It is a side view of the laminated tablet which concerns on one Embodiment of this invention. (B) is a vertical cross-sectional view of FIG. 1 (a).

(Laminated tablets)
The laminated tablet of the present invention includes a first layer and a second layer adjacent to the first layer.
A laminated tablet according to an embodiment of the present invention will be described with reference to FIG.

The laminated tablet 1 of FIG. 1 includes a first layer 10 and a second layer 20.
The first layer 10 and the second layer 20 are in contact with each other at the boundary surface 32. That is, the second layer 20 is adjacent to the first layer 10.
The laminated tablet 1 has a substantially columnar shape. The surface (top surface) 22 of the second layer 20 opposite to the boundary surface 32 is a curved surface that bulges upward from the peripheral edge toward the center. The surface (bottom surface) 12 of the first layer 10 opposite to the boundary surface 32 is a curved surface that bulges downward from the peripheral edge toward the center. The laminated tablet 1 is a so-called two-stage R tablet.
As shown in FIG. 1B, the boundary surface 32 has the same shape as the top surface 22. In the laminated tablet 1, in the production method described later, the first powder constituting the first layer 10 is pressed by a punch (first compression step), and then the second layer 20 is applied to the first powder. The second powder constituting the above is placed, and these are pressed by a punch having the same shape as that of the first compression step. Therefore, the boundary surface 32 has the same shape as the top surface 22.
As shown in FIG. 1A, a boundary line 30 is formed at the boundary between the first layer 10 and the second layer 20 in a side view.

The size of the laminated tablet 1 is not particularly limited. The diameter R of the laminated tablet 1 is, for example, preferably 6 to 13 mm, more preferably 7 to 10 mm, and even more preferably 7 to 9 mm.
The height H of the laminated tablet 1 is preferably, for example, 3 to 10 mm, more preferably 3 to 7 mm.
The degree of swelling of the top surface 22 (cap height h2) is not particularly limited, and is preferably 1 to 2 mm, for example. When the cap height h2 is within the above range, delamination between the first layer 10 and the second layer 20 can be suppressed more satisfactorily. The degree of swelling of the bottom surface 12 (cap height h1) is the same as that of the cap height h2. The cap height h1 and the cap height h2 may be the same or different.
The mass of the laminated tablet 1 is not particularly limited, and is preferably 150 to 550 mg, for example.

The laminated tablet 1 contains at least one (α) component selected from the following (A) component and the following (B) component.
(A) Ingredient: At least one selected from dry aluminum hydroxide gel, aluminum glycinate, magnesium carbonate, magnesium oxide, magnesium aluminometasilicate, synthetic hydrotalcite, glycine and sucralfate.
(B) Ingredient: At least one selected from loxoprofen and its salt.

In the present embodiment, the component (α) may be contained in both or one of the first layer 10 and the second layer 20. Since the component (α) is contained in both or one of the first layer 10 and the second layer 20, the first layer 10 and the second layer 20 are less likely to be peeled off at the boundary surface 32. (Delamination is unlikely to occur).

The component (A) is at least one selected from dry aluminum hydroxide gel, aluminum glycinate, magnesium carbonate, magnesium oxide, magnesium aluminometasilicate, synthetic hydrotalcite, glycine and sucralfate. Among them, as the component (A), dry aluminum hydroxide gel and magnesium oxide are preferable from the viewpoint of suppressing gastric disorders and better suppressing delamination.
The component (A) may be used alone or in combination of two or more.

The component (A) may be contained only in the first layer 10, may be contained only in the second layer 20, or may be contained in both the first layer 10 and the second layer 20. It may be contained.

The component (B) is at least one selected from loxoprofen and a salt thereof. The salt of loxoprofen may be any pharmaceutically acceptable salt, and examples thereof include alkali metal salts such as sodium salt and potassium salt, and alkaline earth metal salts such as calcium salt.
The component (B) may be a hydrate or an anhydrate. Examples of the hydrate of the component (B) include loxoprofen sodium dihydrate. The water content of the raw powder of loxoprofen sodium dihydrate is 11 to 13% by mass. Therefore, it is effective in improving tablet strength and suppressing delamination.
As the component (B), a salt of loxoprofen is preferable, and sodium loxoprofen is more preferable.
The component (B) may be used alone or in combination of two or more.

The component (B) may be contained only in the first layer 10, may be contained only in the second layer 20, or may be contained in both the first layer 10 and the second layer 20. It may be contained.

The component (A) and the component (B) may both be contained in the first layer 10, both may be contained in the second layer 20, or each may be contained in another layer. Good. Above all, it is preferable that the component (A) and the component (B) are contained in different layers. Since the component (A) and the component (B) are contained in separate layers, it is possible to suppress discoloration and compounding change caused by contact between the component (A) and the component (B). Delamination between the layer 10 and the second layer 20 can be suppressed more satisfactorily.

When the first layer 10 contains the (α) component, the content of the (α) component in the first layer 10 is preferably 10 to 80% by mass, more preferably 20 to 80% by mass, and 30 to 80% by mass. 80% by mass is more preferable, and 45 to 80% by mass is particularly preferable. When the content of the component (α) is at least the above lower limit value, delamination between the first layer 10 and the second layer 20 can be suppressed more satisfactorily. When the content of the component (α) is not more than the above upper limit value, it is possible to better suppress the powder (first powder) constituting the first layer 10 from adhering to the molding machine during manufacturing. ..

When the second layer 20 contains the (α) component, the content of the (α) component in the second layer 20 is the same as the content of the (α) component in the first layer 10 described above. is there.

When the first layer 10 and the second layer 20 contain the (α) component, the content of the (A) component in each layer is the content of the (α) component in the first layer 10 described above. Similar to quantity. In this case, the content of the (α) component in the first layer 10 and the content of the (α) component in the second layer 20 may be the same or different.

The component (α) may be contained in the first layer 10 or the second layer 20. However, from the viewpoint of suppressing the powder constituting the upper layer (second layer) from adhering to the punch and causing a locking disorder during tableting molding, the first layer 10 contains the component (A). It is preferable that the second layer 20 contains the component (B) and does not contain the component (A). By containing the component (A) and the component (B) in different layers, it is possible to suppress a change in composition or discoloration due to contact between the component (A) and the component (B). In addition, since the lower first layer 10 contains the component (A), delamination between the first layer 10 and the second layer 20 can be suppressed more satisfactorily.

When the first layer 10 contains the component (α), the water content of the first layer 10 is not particularly limited, but is preferably 2 to 13% by mass, for example.
When the first layer 10 contains the component (A) and does not contain the component (B), the water content of the first layer 10 is preferably 5 to 13% by mass, more preferably 6.5 to 12% by mass. It is preferable, and 7 to 10% by mass is more preferable.
When the first layer 10 contains the component (B) and does not contain the component (A), the water content of the first layer 10 is preferably 2 to 12% by mass, more preferably 4 to 10% by mass. 6 to 10% by mass is more preferable.
When the water content is at least the above lower limit value, delamination between the first layer 10 and the second layer 20 can be suppressed more satisfactorily. When the water content is not more than the above upper limit value, discoloration on the boundary surface 32 can be satisfactorily suppressed.
The water content is a value calculated from the weight loss by drying when heated at 120 ° C. for 10 minutes with an electronic moisture meter (MOISTURE BALANCE MOC-120H, manufactured by Shimadzu Corporation).

When the second layer 20 contains the component (α), the water content of the second layer 20 is the same as the water content of the first layer 10.

When the first layer 10 and the second layer 20 contain the component (α), the water content of the first layer 10 and the water content of the second layer 20 may be the same or different. You may.

The laminated tablet 1 may contain an arbitrary component other than the component (α). The optional component may be contained in a layer containing the component (α) or may be contained in a layer not containing the component (α).

Examples of the optional component include physiologically active substances (arbitrary drugs) other than the component (B); additives such as binders, excipients, disintegrants, flavors, pigments, lubricants, sweeteners, acidulants, etc.; Can be mentioned.
Optional drugs include antipyretic and analgesic components other than component (B) (eg, pyroxycam, meroxycam, ampyroxycam, serocoxib, lofecoxib, thialamide, acetaminophen, etenzamid, sulpyrine, etc.), sedative and hypnotic components (eg, allylisopropylacetylurea). , Bromvalerylurea, etc.), antihistamine components (eg, isotipendyl hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, dipheterol hydrochloride, tryprolysine hydrochloride, triperenamine hydrochloride, tonzilamine hydrochloride, phenetazine hydrochloride, metodilazine hydrochloride, diphenyldisulfonate carbinoxamine Alimemazine, diphenhydramine tannate, diphenylpyraline theocrate, mebuhydroline napadisylate, promethazine methylene disalicylate, carbinoxamine maleate, chlorpheniramine dl-chlorpheniramine maleate, chlorpheniramine d-maleate, diferrol phosphate, etc.) (For example, sodium benzoate caffeine, caffeine, anhydrous caffeine, etc.), antitussive sputum components (codein phosphate, dextrometorfan hydrobromide bromide, dimemorphan phosphate, tipepidin hibenzate, methoxyphenamine) Hydrochloride, trimetoxinol hydrochloride, carbocysteine, acetylcysteine, ethylcysteine, dl-methylephedrine, bromhexin hydrochloride, therapeptase, lysozyme chloride, ambroxol, theophylline, aminophyllin), vitamin components (eg, vitamin B1 and its) Derivatives and their salts, vitamin B2 and its derivatives and their salts, vitamin C and its derivatives and their salts, hesperidin and its derivatives and their salts, etc.) and the like. These arbitrary drugs may be used alone or in combination of two or more.

Examples of the binder include starch, pregelatinized starch, sucrose, gelatin, gum arabic powder, polyvinylpyrrolidone, pullulan, dextrin and the like.
Examples of the excipient include crystalline cellulose, lactose (including lactose hydrate and lactose granules), cornstarch, powdered sugar, mannitol, L-cysteine and the like.
Examples of the disintegrant include low-degree-of-substitution hydroxypropyl cellulose, crospovidone, croscarmellose sodium, partially pregelatinized starch and the like.
Examples of the lubricant include magnesium stearate, stearyl sodium fumarate, sucrose fatty acid ester, and light anhydrous silicic acid.
Examples of the fragrance include menthol, limonene, vegetable essential oil (mentha oil, mint oil, lychee oil, orange oil, lemon oil, etc.) and the like.
Examples of the sweetener include sodium saccharin, aspartame, stevia, dipotassium glycyrrhizinate, acesulfame potassium, thaumatin, sucralose and the like.
Examples of the acidulant include citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, lactic acid, and salts thereof.
Examples of the pigment include iron sesquioxide and the like.

Among the above-mentioned additives, optional components coexisting with the component (B) include lactose hydrate, lactose granules, mannitol, crystalline cellulose, light anhydrous silicic acid, iron sesquioxide, and low-substituted hydroxypropyl. Lactose is preferred, lactose hydrate, lactose granules, low-substituted dehydroxypropyl cellulose, iron sesquioxide are more preferred, lactose hydrate or lactose granules, and iron sesquioxide and low-substituted hydroxypropyl cellulose. The combination with the mixture is more preferred.

Among the above-mentioned additives, lactose hydrate, lactose granules, mannitol, light anhydrous silicic acid, and low-substituted hydroxypropyl cellulose are preferable, and lactose hydration is preferable as an optional component coexisting with the component (A). Products, lactose granules, and low-substituted hydroxypropyl cellulose are more preferred, and lactose hydrates or lactose granules in combination with low-substituted hydroxypropyl cellulose are even more preferred.

(Manufacturing method of laminated tablets)
The method for producing a laminated tablet of the present invention is a production method by a tableting molding method, and includes a first compression step and a second compression step.

An example of this manufacturing method will be described.
In the manufacturing method of this example, a tableting machine provided with a punch and a mortar is used to beat the first powder constituting the first layer 10 and the second powder constituting the second layer 20. Lock.
In this example, both or one of the first powder and the second powder contains the component (α).

In the first compression step in the manufacturing method of this example, the first powder is put into a mortar, a pestle is inserted into the mortar, and the first powder in the mortar is compressed at an arbitrary pressure. The first compression step of the present embodiment is a so-called precompression step.

Examples of the first powder include powders containing the component (α). Since the first powder constitutes the first layer 10 which is the lower layer, it is preferable that the first powder contains the component (A) and does not contain the component (B). By using such a first powder, adhesion of the first powder into the mortar can be suppressed.
When the first powder contains the component (α), the water content of the first powder is preferably, for example, 2 to 13% by mass.
When the first powder contains the component (A) and does not contain the component (B), the water content of the first powder is preferably 5 to 13% by mass, more preferably 6.5 to 12% by mass. It is preferable, and 7 to 10% by mass is more preferable.
When the first powder contains the component (B) and does not contain the component (A), the water content of the first powder is preferably 2 to 12% by mass, more preferably 4 to 10% by mass. 6 to 10% by mass is more preferable.
When the water content is at least the above lower limit value, delamination between the first layer 10 and the second layer 20 can be suppressed more satisfactorily. When the water content is not more than the above upper limit value, discoloration on the boundary surface 32 can be satisfactorily suppressed.

The pressure in the first compression step (first compression pressure) is appropriately determined in consideration of the composition of the first powder, the size of the laminated tablet, and the like. For example, in the case of producing a laminated tablet having a diameter R of 8 to 9 mm and a height H of 4 to 8 mm, the first compression pressure is about 1 to 3 kN. When the first compression pressure is equal to or higher than the above lower limit value, the first powder forms a mass having an appropriate strength, so that the first layer 10 and the second layer 20 can be easily formed in the second compression step. Can be formed beautifully. When the first compression pressure is not more than the above upper limit value, delamination between the first layer 10 and the second layer 20 can be suppressed more satisfactorily.

In the second compression step in the manufacturing method of this example, after the first compression step, the second powder is put in the mortar, and the first powder and the second powder in the mortar are compressed. The first layer 10 and the second layer 20 are formed. That is, the second compression step of the present embodiment is the so-called main compression step.

Examples of the second powder include powders containing the component (α). Since the second powder constitutes the second layer 20 which is the upper layer, it is preferable that the second powder contains the component (B) and does not contain the component (A). By using such a second powder, the adhesion between the first layer 10 and the second layer 20 can be improved while suppressing the adhesion of the first and second powders to the mortar and pestle. Can be enhanced.
When the second powder contains the component (α), the water content of the second powder is the same as the water content of the first powder.
When the first powder and the second powder contain the component (α), the water content of the first powder and the water content of the second powder may be the same or different. You may.

The pressure in the second compression step (second compression pressure) may be higher than the first compression pressure, and is appropriately determined in consideration of the composition of the second powder, the size of the laminated tablet, and the like. .. For example, when producing a laminated tablet having a diameter R of 8 to 9 mm and a height H of 4 to 8 mm, the second compression pressure is preferably, for example, more than 3 kN, more preferably 5 to 15 kN. When the second compression pressure is at least the above lower limit value, delamination between the first layer 10 and the second layer 20 can be suppressed more satisfactorily. When the second compression pressure is not more than the above upper limit value, the laminated tablet 1 having an appropriate hardness can be produced, and the laminated tablet 1 can be prevented from being damaged during the production.

An intermediate compression step may be provided between the first compression step and the second compression step. The intermediate compression step is a step of placing the second powder on the first powder and compressing the second powder at a pressure higher than the first compression pressure and lower than the second compression pressure. By providing the intermediate compression step, when the first layer 10 and the second layer 20 have different color tones, the boundary line 30 becomes clear and the appearance becomes beautiful. Further, when the components contraindicated for compounding are separately compounded in the first layer 10 and the second layer 20, the contact area between the two layers is reduced and the stability of the components contraindicated for compounding is enhanced.
The pressure in the intermediate compression step is, for example, 1 to 4 kN.

Whether or not the laminated tablet 1 is produced by a production method including the first compression step can be specified by, for example, the following exposure test. The tablets are exposed to the environment at 50 ° C. and 75% RHS for 3 days to discolor the first layer 10 or the second layer 20. Observe the borders of the exposed tablets. Those with straight boundaries are manufactured by a manufacturing method including a first compression step. Those having a distorted boundary line are manufactured by a manufacturing method that does not include the first compression step.
Alternatively, the first compression step is performed by dropping the tablet onto a hard surface, peeling the first layer and the second layer, and observing the interface between the first layer and the second layer. It can be determined whether or not it was manufactured by the manufacturing method having. Those having the same shape as the top surface of the second layer at the boundary surface are manufactured by a manufacturing method including the first compression step. If the boundary surface has a shape different from that of the top surface of the second layer, it is manufactured by a manufacturing method that does not include the first compression step.

The laminated tablet 1 in which the first layer 10 and the second layer 20 are formed through the first compression step and the second compression step may be subjected to a coating treatment, if necessary.
The coating agent used in the coating treatment may be any as long as it does not significantly impair the disintegration property of the laminated tablet 1, and examples thereof include water-soluble polymer compounds and plasticizers.
As a coating agent, celluloses such as carmellose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, low substitution hydroxypropyl cellulose, hydroxymethyl cellulose, methyl cellulose, ethyl cellulose; arabic rubber, carboxyvinyl polymer, povidone, crospovidone, polyvinyl alcohol, polysaccharide Acids, monosaccharides, polysaccharides of disaccharide or higher (sugar (granule sugar, etc.), lactose hydrate, malt sugar, xylose, isomerized lactose, etc.), sugar alcohols (palatinit, sorbitol, lactitol, erythritol, xylitol, reduced starch saccharification) Products, martitol, mannitol, etc.), water candy, isomerized saccharides, oligosaccharides, sucrose, trehalose, reduced starch saccharified product (reduced starch decomposition product), and the like.
Examples of the plasticizer include those described in the Japanese Pharmacopoeia (Hirokawa Shoten) such as triethyl citrate and triacetin and official documents such as the Pharmaceutical Additives Standard (Yakuji Nippo Co., Ltd.).
These coating agents may be used alone or in combination of two or more.

Since the above-mentioned laminated tablet contains the component (α) in both or one of the adjacent first layer and the second layer, the laminated tablet produced by a production method including a precompression step has layers. Less likely to peel off.

The laminated tablet of the present invention contains a component (A) and a component (B), and at least one of the first layer and / or the second layer is selected from the component (A) and the component (B). As long as it contains the (α) component of the seed, it is not limited to the above-described embodiment.

In the above-described embodiment, the laminated tablet is a two-stage R tablet having a circular shape in a plan view, but the present invention is not limited to this, and the laminated tablet may be a circular Sumi square tablet, a circular Sumi round tablet, or the like. The circular sumi square tablet is a tablet having a shape in which the peripheral edges of both end faces of a cylinder are chamfered with a straight line. The circular Sumi round tablet is a tablet having a shape in which the periphery of both end faces of a cylinder is chamfered with R faces.
Further, for example, the laminated tablet is not limited to a circular shape in a plan view, and may be a polygon in a plan view.

In the above-described embodiment, the laminated tablet has a two-layer structure of a first layer and a second layer, but the present invention includes an adjacent first layer and a second layer. Not limited to. For example, another layer may be formed on the opposite side of the second layer in the first layer, or another layer may be formed on the opposite side of the first layer in the second layer. May be good.

In the above-described embodiment, the cross-sectional shape of the boundary surface and the cross-sectional shape of the top surface are the same, but the present invention is not limited to this. For example, when the shape of the pestle used in the first compression step and the shape of the pestle used in the second compression step are different, the cross-sectional shape of the boundary surface and the cross-sectional shape of the top surface are different.

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to the following description.

(Raw materials used)
<Ingredient (A)>
-Dry aluminum hydroxide gel (manufactured by Kyowa Chemical Industry Co., Ltd.).
-Magnesium oxide (manufactured by Tomita Pharmaceutical Co., Ltd.).
-Magnesium carbonate (manufactured by Kyowa Chemical Industry Co., Ltd.).
-Synthetic hydrotalcite (manufactured by Kyowa Chemical Industry Co., Ltd.).
-Magnesium aluminate metasilicate (manufactured by Fuji Chemical Industries, Ltd.).
-Aluminum glycinate (manufactured by Kyowa Chemical Industry Co., Ltd.).
・ Sucralfate (manufactured by Fuji Chemical Industries, Ltd.).
-Glycine (manufactured by Kanto Chemical Co., Inc.).
<Ingredient (B)>
-Loxoprofen sodium dihydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd.).
<Arbitrary ingredient>
-Acetaminophen (manufactured by Iwaki Pharmaceutical Co., Ltd.).
-Allyl isopropyl acetyl urea (manufactured by Kongo Chemical Co., Ltd.).
-Anhydrous caffeine (manufactured by Shiratori Pharmaceutical Co., Ltd.).
-Ibuprofen (manufactured by BASF).
-Lactose hydrate (manufactured by DFE Pharma).
-Lactose granulated product (manufactured by Freund Sangyo Co., Ltd.).
-Low degree of substitution hydroxypropyl cellulose (L-HPC, manufactured by Shin-Etsu Chemical Co., Ltd.).
-Magnesium stearate (manufactured by Taihei Kagaku Sangyo Co., Ltd.).

(Evaluation method)
<Delamination immediately after locking>
Using an abrasion degree tester (manufactured by Toyama Sangyo Co., Ltd.), 20 tablets immediately after tableting in each example were rotated at 25 rpm for 10 minutes. The tablets were observed after the rotation was completed, and the number of tablets that had delaminated was counted. The number of tablets with delamination was evaluated by classifying them according to the following evaluation criteria. Those with an evaluation result of 3 points or more were judged to pass.

≪Evaluation criteria≫
6 points: There are no tablets that have undergone delamination.
5 points: 1-2 tablets with delamination.
4 points: 3 to 6 tablets with delamination.
3 points: 7 to 10 tablets with delamination.
2 points: 11 to 15 tablets with delamination.
1 point: 16 or more tablets with delamination.

<Delamination after storage>
The tablets 25 of each example were subjected to PTP (Press Through Package) packaging (individual packaging). Tablets with PTP packaging were stored at 40 ° C. and 75% RH for 1 week. Delamination was evaluated in the same manner as in "<< Delamination immediately after tableting >>" except that the tablets stored for 1 week were used.

(Examples 1-31 and Comparative Examples 1-7)
According to the compositions of Tables 1 to 8, the powder constituting the first layer (first powder) and the powder constituting the second layer (second powder) were prepared. The first powder and the second powder were tableted under the following tableting conditions to obtain tablets of each example. The obtained tablets were evaluated for delamination immediately after tableting and delamination after storage, and the results are shown in the table.
The water content of the layer containing the component (α) in the tablets of each example was 2.5 to 12% by mass.

(Locking conditions)
-Locking machine: Rotary type locking machine Libra 3L (manufactured by Kikusui Seisakusho Co., Ltd.).
-Board rotation speed: 20 rpm.
-Usuki: φ8.5 mm (two-stage R) x 12 stands, no marking (cap height h1 and h2 = 0.1 mm, radius of curvature at the boundary between the side surface and top surface) = 10, R2 (top surface) Curvature radius) = 3.4).
-First compression pressure: 1 kN (about 10 MPa, about 100 kg / cm ² ).
-Compression pressure in the intermediate compression step: 2 kN (about 20 MPa, about 200 kg / cm ² ).
-Second compression pressure: 10 kN (about 100 MPa, about 1000 kg / cm ² ).

(Examples 32 to 40)
According to the composition of Table 9, each component constituting the first layer is mixed, and the obtained mixed powder is adjusted to have a water content according to the "method for adjusting the water content" in the table. The first powder of "mass of powder (parts by mass)" was obtained.
According to the composition of Table 9, each component constituting the second layer is mixed, and the obtained mixed powder is adjusted to have a water content according to the "method for adjusting the water content" in the table. The second powder of "mass of powder (parts by mass)" was obtained.
Using the obtained first powder and the second powder, tablets of each example were obtained in the same manner as in Example 1. The obtained tablets were evaluated for delamination immediately after tableting and delamination after storage, and the results are shown in the table.
The method for adjusting the water content is as follows.
-Drying: Place the mixed powder on the shelf in the dryer (60 ° C) and leave it for an arbitrary time, then "Mass of the first powder (mass part)" or "Mass of the second powder" in Table 9. The mixture was dried so as to be (part by mass).
-Humidification: Put the mixed powder in an incubator (40 ° C, 75% RH), leave it for an arbitrary time, and in Table 9, "Mass (mass part) of the first powder" or "Second powder". The mixture was humidified to be "body mass (parts by mass)".

As shown in Tables 1 and 2, Examples 1 to 11 in which the first layer contains the component (A) and the second layer contains the component (B) are evaluated for delamination immediately after tableting. The score was 4 to 6 points, and the evaluation of delamination after storage was 3 to 6 points. In particular, when the component (A) containing aluminum was used, the evaluation of delamination was good.
As shown in Table 2, in Examples 12 and 13 in which the first layer contains the component (A), the delamination evaluation immediately after tableting was 4 points, and the delamination evaluation after storage was 3 to 4 points. Met.
As shown in Table 3, in Examples 14 to 16 in which the second layer contains the component (B), the evaluation of delamination immediately after tableting was 3 to 4 points, and the evaluation of delamination after storage was 3 points. Met.
As shown in Tables 4 to 5, in Comparative Examples 1 to 7 in which the first layer and the second layer did not contain the component (A) and the component (B), the delamination immediately after tableting was evaluated from 1 to 7. The evaluation of delamination after storage was 1 to 2 points.

As shown in Table 6, the greater the content of the component (B) in the second layer, the less likely it was that delamination would occur.

As shown in Table 7, the greater the content of the component (A) in the first layer, the less likely it was that delamination would occur.

As shown in Table 8, in Examples 29 to 31, the first layer and the second layer in Examples 1 to 3 are reversed. That is, in Examples 29 to 31, the first layer contains the component (B) and the second layer contains the component (A).
In Examples 29 to 31, the delamination evaluation immediately after tableting was 5 to 6 points, and the delamination evaluation after storage was 4 to 6 points, which were the same results as in the corresponding Examples 1 to 3. .. Among Examples 29 to 31, Example 29 containing the component (A) containing aluminum had a good evaluation of delamination.

As shown in Table 9, the greater the water content of the layer containing the component (α), the less likely it was that delamination would occur. However, in Example 32 in which the water content in the first layer was more than 12% by mass, the boundary between the first layer and the second layer was discolored after storage.

1 laminated tablet, 10 first layer, 12 bottom surface, 20 second layer, 22 top surface, 30 boundary line, 32 boundary surface

Claims (1)

A substantially columnar laminated tablet comprising a first layer and a second layer adjacent to the first layer at a boundary surface.
A laminate characterized in that both or one of the first layer and the second layer contains at least one (α) component selected from the following (A) component and the following (B) component. tablet.
(A) Ingredient: At least one selected from dry aluminum hydroxide gel, aluminum glycinate, magnesium carbonate, magnesium oxide, magnesium aluminometasilicate, synthetic hydrotalcite, glycine and sucralfate.
(B) Ingredient: At least one selected from loxoprofen and its salt.

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