JP7209537B2 - Solid pharmaceutical formulation - Google Patents

Description

The present invention relates to solid pharmaceutical formulations.

Non-steroidal anti-inflammatory drugs (NSAIDs) and the like are widely used as antipyretic analgesic ingredients in pharmaceutical formulations such as antipyretic analgesics.
NSAIDs can cause stomach upset (stomach disorder). Pharmaceutical formulations containing antacids are known for the purpose of suppressing stomach disorders. For example, US Pat. No. 6,300,000 discloses formulations consisting of a combination of NSAIDs and antacids.

JP-A-4-230330

By the way, therapeutic ingredients for both or one of the digestive organs and digestive system (eg, antacids, gastric acid secretion inhibitors, muscarinic receptor antagonists, protective factor promoters, etc.) absorb moisture over time. If the disease-treating ingredient, etc. in the solid pharmaceutical preparation absorbs moisture, it may become difficult to disperse the disease-treating ingredient, etc. in the solid pharmaceutical preparation after administration (decrease in dispersibility), or the solid pharmaceutical preparation may become difficult to disintegrate (disintegration). decrease). When the dispersibility and disintegration are lowered, it is difficult for the pharmaceutical preparation to immediately exhibit its pharmacological action.
Accordingly, an object of the present invention is to provide a solid pharmaceutical formulation that is less likely to absorb moisture.

The present invention has the following aspects.
[1] A solid pharmaceutical containing a therapeutic component (A) for both or one of digestive organs and digestive system and at least one drug (B) selected from meloxicam and its pharmaceutically acceptable salts. pharmaceutical formulation.
[2] Component (A) includes dried aluminum hydroxide gel, glycine, magnesium silicate, aluminum hydroxide gel, aluminum hydroxide-magnesium carbonate co-dried gel, aluminum hydroxide-sodium bicarbonate co-precipitate, hydroxide A first antacid (a1) which is at least one selected from aluminum-calcium carbonate-magnesium carbonate co-precipitate, magnesium hydroxide-aluminum potassium sulfate co-precipitate and magnesium carbonate,
The solid pharmaceutical preparation according to [1], wherein the mass ratio represented by component (B)/component (a1) is 0.01 to 0.25.
[3] The component (A) is magnesium oxide (a2),
The solid pharmaceutical preparation according to [1], wherein the mass ratio represented by component (B)/component (a2) is 0.02 to 0.4.
[4] The component (A) is magnesium aluminometasilicate (a3),
The solid pharmaceutical preparation according to [1], wherein the mass ratio represented by component (B)/component (a3) is 0.0067 to 0.25.
[5] The component (A) is synthetic aluminum silicate (a4),
The solid pharmaceutical preparation according to [1], wherein the mass ratio of component (B)/component (a4) is 0.0033 to 0.067.
[6] The component (A) is dihydroxyaluminumaminoacetic acid (a5),
The solid pharmaceutical preparation according to [1], wherein the mass ratio represented by component (B)/component (a5) is 0.0067 to 0.33.
[7] The component (A) is a synthetic hydrotalcite (a6),
The solid pharmaceutical preparation according to [1], wherein the mass ratio represented by component (B)/component (a6) is 0.0025 to 0.1.
[8] The solid pharmaceutical preparation according to [1], wherein the component (A) is a protective factor enhancer (a10).

[9] The component (A) is at least one selected from magnesium aluminosilicate, magnesium aluminum hydroxide, magnesium hydroxide, sodium hydrogen carbonate, precipitated calcium carbonate, anhydrous dicalcium phosphate, and calcium hydrogen phosphate. The solid pharmaceutical preparation according to [1], which is an antacid (a7) of
[10] The solid pharmaceutical preparation according to [1], wherein the component (A) is a gastric acid secretion inhibitor (a8).
[11] The solid pharmaceutical preparation according to [1], wherein the component (A) is a muscarinic receptor antagonist (a9).

[12] The solid pharmaceutical preparation according to any one of [1] to [11], which is a tablet, capsule, pill, granule, powder or fine granule.
[13] The solid pharmaceutical preparation according to any one of [1] to [12], wherein the content of component (B) is 1 to 25% by mass.

According to the solid pharmaceutical formulation of the present invention, it is possible to suppress moisture absorption.

FIG. 2 is a side view showing an example of a tablet (standard R tablet or sugar-coated R tablet). Fig. 10 is a side view showing another example of a tablet (two-stage R tablet); Fig. 10 is a side view showing another example of a tablet (round square flat tablet). FIG. 10 is a side view showing another example of a tablet (round round flat tablet).

(Solid pharmaceutical formulation)
The solid pharmaceutical preparation of the present invention comprises at least one selected from therapeutic ingredients (A) (ingredient (A)) for both or one of digestive organs and digestive system, and meloxicam and pharmaceutically acceptable salts thereof. drug (B) (component (B)).

<(A) Component>
The component (A) is a therapeutic component for both or one of the digestive organs and the digestive system, and is also called a gastrointestinal drug component. Preferred components (A) are antacids, gastric acid secretion inhibitors, muscarinic receptor antagonists, and protective factor promoters. The component (A) may be a compound listed in the Japanese Pharmacopoeia 17th Edition or the Pharmaceutical Standards outside the Japanese Pharmacopoeia.
Component (A) includes dried aluminum hydroxide gel, glycine, magnesium silicate, aluminum hydroxide gel, aluminum hydroxide-magnesium carbonate co-dried gel, aluminum hydroxide-sodium bicarbonate co-precipitate, aluminum hydroxide-carbonic acid. Calcium-magnesium carbonate coprecipitate, magnesium hydroxide-potassium aluminum sulfate coprecipitate, magnesium carbonate (hereinafter sometimes referred to as first antacid (a1) (component (a1))); magnesium oxide (a2) ((a2) component); magnesium aluminometasilicate (magnesium aluminometasilicate) (a3) ((a3) component); synthetic aluminum silicate (a4) ((a4) component); dihydroxyaluminum aminoacetic acid (a5) ( (a5) component); synthetic hydrotalcite (a6) ((a6) component); magnesium aluminosilicate, magnesium aluminum hydroxide, magnesium hydroxide, sodium hydrogen carbonate, precipitated calcium carbonate, anhydrous dicalcium phosphate, calcium hydrogen phosphate (These are sometimes referred to as second antacids (a7) (ingredient (a7))); (These are sometimes referred to as gastric acid secretion inhibitors (a8) (component (a8))); pirenzepine, atropine, scopolamine (these are sometimes referred to as muscarinic receptor antagonists (a9) (component (a9))) ); sucralfate, aldioxa, azulene, L-glutamine, rebamipide (these may be referred to as protective factor promoter (a10) (component (a10)))). Among them, the components (a1) to (a6) and (a8) to (a10) are preferable as the component (A).
(A) Component may be used individually by 1 type, and may be used in combination of 2 or more types.

The content of component (A) in the solid pharmaceutical preparation is determined in consideration of the type and effective amount of component (A), the content of component (B), and the like.

<(B) Component>
Component (B) is meloxicam (chemical name: 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) and At least one drug selected from the group consisting of pharmaceutically acceptable salts thereof. Pharmaceutically acceptable salts of meloxicam are described, for example, in EP 0,002,482 B1, US Pat. No. 4,233,299 and WO 99/49867. things are mentioned. Acceptable salts include sodium, potassium, ammonium, meglumine, tris salts and the like.
The component (B) may be used singly or in combination of two or more.
A solid pharmaceutical preparation can suppress moisture absorption by including the component (B). The component (B) is conventionally known as an oxicam-based non-steroidal anti-inflammatory drug that has a selective COX-2 inhibitory effect and is effective for arthralgia, lumbago, stiff shoulder pain, and the like. However, it has not been known until now that component (B) can suppress moisture absorption.

The content of component (B) in the solid pharmaceutical preparation is preferably such that the amount of component (B) per dose is 0.5 to 70 mg, more preferably 2.5 to 50 mg, and 5 to 10 mg. is more preferred, and 10 mg is most preferred. When the content of component (B) is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of component (B) is at least the above lower limit, problems during tablet production (for example, adhesion of the pharmaceutical composition to the discs and punches of a tableting machine, etc.) are less likely to occur.

The content of component (B) in the solid pharmaceutical formulation is, for example, preferably 1 to 25% by mass, more preferably 1.5 to 15% by mass, even more preferably 2 to 10% by mass. If the content of component (B) is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of component (B) is equal to or less than the above upper limit, friability can be suppressed when the solid pharmaceutical preparation is a tablet.

The content of component (A) in the solid pharmaceutical formulation is determined in consideration of the type of component (A).
In the solid pharmaceutical formulation, the mass ratio represented by component (B)/component (A) (hereinafter referred to as B/A ratio) is appropriately determined in consideration of the type of component (A). The B/A ratio is the mass ratio of component (B) to component (A).

When component (A) is component (a1), the content of component (a1) is preferably 40 to 1000 mg, more preferably 60 to 350 mg, even more preferably 70 to 350 mg. If the content of component (a1) is equal to or less than the above upper limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of component (a1) is at least the above lower limit, gastric disorders can be suppressed more satisfactorily.
In the solid pharmaceutical formulation, the lower limit of the mass ratio (B/a1 ratio) represented by component (B)/component (a1) is preferably 0.01 or more, more preferably 0.014 or more, and 0.029 or more. is more preferred. The upper limit of B/a1 is preferably 0.25 or less, more preferably 0.17 or less, and even more preferably 0.14 or less. When the B/a1 ratio is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the B/a1 ratio is equal to or less than the above upper limit, gastric disorders can be suppressed more satisfactorily, and friability can be suppressed when the solid pharmaceutical preparation is a tablet.

When component (A) is component (a2), the content of component (a2) is preferably 25 to 500 mg, more preferably 30 to 65 mg, even more preferably 33 to 60 mg. If the content of the component (a2) is equal to or less than the above upper limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of component (a2) is at least the above lower limit, gastric disorders can be suppressed more satisfactorily.
In the solid pharmaceutical formulation, the lower limit of the mass ratio (B/a2 ratio) represented by component (B)/component (a2) is preferably 0.02 or more, more preferably 0.083 or more, and 0.15 or more. is more preferred, and 0.17 or more is most preferred. The upper limit of the B/a2 ratio is preferably 0.4 or less, more preferably 0.33 or less, and even more preferably 0.3 or less. If the B/a2 ratio is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the B/a2 ratio is equal to or less than the above upper limit, gastric disorders can be suppressed more satisfactorily, and friability can be suppressed when the solid pharmaceutical preparation is a tablet.

When component (A) is component (a3), the content of component (a3) is preferably 40 to 1500 mg, more preferably 80 to 200 mg, even more preferably 90 to 150 mg. If the content of component (a3) is equal to or less than the above upper limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of component (a3) is at least the above lower limit, gastric disorders can be suppressed more satisfactorily.
In the solid pharmaceutical preparation, the lower limit of the mass ratio represented by component (B)/component (a3) (B/a3 ratio) is preferably 0.0067 or more, more preferably 0.033 or more, and 0.05 or more. is more preferred, and 0.067 or more is most preferred. The upper limit of the B/a3 ratio is preferably 0.25 or less, more preferably 0.13 or less, and even more preferably 0.11 or less. If the B/a3 ratio is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the B/a3 ratio is equal to or less than the above upper limit, gastric disorders can be suppressed more satisfactorily, and friability can be suppressed when the solid pharmaceutical preparation is a tablet.

When component (A) is component (a4), the content of component (a4) is preferably 150-3000 mg, more preferably 190-2000 mg, and even more preferably 250-400 mg. If the content of component (a4) is equal to or less than the above upper limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of component (a4) is at least the above lower limit, gastric disorders can be better suppressed.
In the solid pharmaceutical preparation, the lower limit of the mass ratio represented by component (B)/component (a4) (B/a4 ratio) is preferably 0.0033 or more, more preferably 0.00125 or more, and 0.005 or more. is more preferred, and 0.025 or more is most preferred. The upper limit of the B/a4 ratio is preferably 0.067 or less, more preferably 0.053 or less, and even more preferably 0.04 or less. When the B/a4 ratio is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the B/a4 ratio is equal to or less than the above upper limit, gastric disorders can be suppressed more satisfactorily, and friability can be suppressed when the solid pharmaceutical preparation is a tablet.

When component (A) is component (a5), the content of component (a5) is preferably 30 to 1500 mg, more preferably 50 to 120 mg, even more preferably 70 to 110 mg. If the content of component (a5) is equal to or less than the above upper limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of component (a5) is at least the above lower limit, gastric disorders can be better suppressed.
In the solid pharmaceutical preparation, the lower limit of the mass ratio represented by component (B)/component (a5) (B/a5 ratio) is preferably 0.0067 or more, more preferably 0.045 or more, and 0.083 or more. is more preferred, and 0.091 or more is most preferred. The upper limit of the B/a5 ratio is preferably 0.33 or less, more preferably 0.2 or less, and even more preferably 0.14 or less. If the B/a5 ratio is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the B/a5 ratio is equal to or less than the above upper limit, gastric disorders can be better suppressed, and friability can be suppressed when the solid pharmaceutical preparation is a tablet.

When component (A) is component (a6), the content of component (a6) is preferably 100 to 4000 mg, more preferably 200 to 1000 mg, even more preferably 250 to 400 mg. If the content of component (a6) is equal to or less than the above upper limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of component (a6) is at least the above lower limit, gastric disorders can be suppressed more satisfactorily.
In the solid pharmaceutical preparation, the lower limit of the mass ratio represented by component (B)/component (a6) (B/a6 ratio) is preferably 0.0025 or more, more preferably 0.01 or more, and 0.0125 or more. is more preferred, and 0.025 or more is most preferred. The upper limit of the B/a6 ratio is preferably 0.1 or less, more preferably 0.05 or less, and even more preferably 0.04 or less. If the B/a6 ratio is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the B/a6 ratio is equal to or less than the above upper limit, gastric disorders can be suppressed more satisfactorily, and friability can be suppressed when the solid pharmaceutical preparation is a tablet.

When component (A) is component (a7), the content of component (a7) is preferably 30 to 2000 mg, more preferably 60 to 1000 mg, even more preferably 80 to 500 mg. If the content of component (a7) is equal to or less than the above upper limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of component (a7) is at least the above lower limit, gastric disorders can be suppressed more satisfactorily.
In the solid pharmaceutical preparation, the lower limit of the mass ratio represented by component (B)/component (a7) (B/a7 ratio) is preferably 0.005 or more, more preferably 0.01 or more, and 0.02 or more. is more preferred. The upper limit of the B/a7 ratio is preferably 0.33 or less, more preferably 0.17 or less, and even more preferably 0.125 or less. If the B/a7 ratio is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the B/a7 ratio is equal to or less than the above upper limit, gastric disorders can be suppressed more satisfactorily, and friability can be suppressed when the solid pharmaceutical preparation is a tablet.

When component (A) is component (a8), the content of component (a8) is preferably 1 to 500 mg, more preferably 5 to 400 mg. If the content of the component (a8) is equal to or less than the above upper limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of component (a8) is at least the above lower limit, the secretion of gastric acid can be better suppressed.
In the solid pharmaceutical preparation, the lower limit of the mass ratio represented by component (B)/component (a8) (B/a8 ratio) is preferably 0.00625 or more, more preferably 0.02 or more, and 0.025 or more. is more preferred. The upper limit is preferably 10 or less, more preferably 2 or less. If the B/a8 ratio is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the B/a8 ratio is equal to or less than the above upper limit, gastric acid secretion can be better suppressed, and friability can be suppressed when the solid pharmaceutical preparation is a tablet.

When component (A) is component (a9), the content of component (a9) is preferably 0.01 to 100 mg, more preferably 0.1 to 50 mg. If the content of component (a9) is equal to or less than the above upper limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. When the content of component (a9) is at least the above lower limit, the stimulation of muscarinic receptors is likely to be inhibited, and the secretion of digestive juices can be better suppressed.
In the solid pharmaceutical preparation, the lower limit of the mass ratio represented by component (B)/component (a9) (B/a9 ratio) is preferably 0.05 or more, more preferably 0.1 or more, and 0.2 or more. is more preferred. The upper limit of B/a9 is preferably 1000 or less, more preferably 500 or less, even more preferably 100 or less. If the B/a9 ratio is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. When the B/a9 ratio is equal to or less than the above upper limit, stimulation of muscarinic receptors is likely to be inhibited, and secretion of digestive juices can be suppressed more satisfactorily, and friability can be suppressed when the solid pharmaceutical preparation is a tablet.

When component (A) is component (a10), the content of component (a10) is preferably 1 to 3000 mg, more preferably 10 to 2000 mg. If the content of the component (a10) is equal to or less than the above upper limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the content of the component (a10) is at least the above lower limit, the gastrointestinal mucosa is easily protected, so gastric disorders can be better suppressed.
In the solid pharmaceutical formulation, the lower limit of the mass ratio (B/a10 ratio) represented by component (B)/component (a10) is preferably 0.00125 or more, more preferably 0.0033 or more, and 0.005 or more. is more preferred. The upper limit of B/a10 is preferably 10 or less, more preferably 5 or less, and even more preferably 1 or less. When the B/a10 ratio is at least the above lower limit, it is possible to further reduce moisture absorption in the solid pharmaceutical preparation. If the B/a10 ratio is equal to or less than the above upper limit, the gastrointestinal mucosa is easily protected, so gastric disorders can be better suppressed, and friability can be suppressed when the solid pharmaceutical preparation is a tablet.

The total amount of components (A) and (B) in the solid pharmaceutical preparation is preferably 10 to 90% by mass, more preferably 20 to 80% by mass, relative to one dose (for example, per tablet). . If the total amount of components (A) and (B) is at least the above lower limit, it is unlikely that one dose will be excessive. If the total amount of component (A) and component (B) is equal to or less than the above upper limit, it is easy to blend a sufficient amount of the optional component described later according to the purpose.

<Optional component>
If necessary, the solid pharmaceutical preparation may further contain other ingredients (optional ingredients) other than the components (A) and (B) within a range that does not impair the effects of the present invention.
Optional components include physiologically active components (excluding components (A) and (B)), additives, and the like.
Examples of physiologically active ingredients include antipyretic analgesic ingredients (excluding (B) ingredient) (for example, piroxicam, ampiroxicam, cerocoxib, rofecoxib, tiaramide, loxoprofen Na, ethenzamide, sulpyrine, acetaminophen, acetylsalicylic acid, etc.). , sedative hypnotic ingredients (e.g., allylisopropylacetylurea, bromvalerylurea, etc.), antihistamine ingredients (e.g., isothipendyl hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, diferol hydrochloride, triprolidine hydrochloride, tripelennamine hydrochloride, tonjilamine hydrochloride, phenetazine hydrochloride, hydrochloric acid methdilazine, diphenhydramine salicylate, carbinoxamine diphenyldisulfonate, arimemazine tartrate, diphenhydramine tannate, diphenylpyraline theocrate, mebhydroline napadisilate, promethazine methylene disalicylate, carbinoxamine maleate, dl-chlorpheniramine maleate, d-chlorphenylate maleate lamin, diferol phosphate, etc.), central stimulant ingredients (e.g., sodium caffeine benzoate, caffeine, anhydrous caffeine, etc.), antitussive expectorant ingredients (codeine phosphate, dextromethorphan hydrobromide, dimemorphan phosphate, etc.) acid, tipepidine hibenzate, methoxyphenamine hydrochloride, trimetoquinol hydrochloride, carbocysteine, acetylcysteine, ethylcysteine, dl-methylephedrine, bromhexine hydrochloride, serrapeptase, lysozyme chloride, ambroxol, theophylline, aminophylline ), vitamin components (e.g. vitamin B ₁ and its derivatives and their salts, vitamin B ₂ and its derivatives and their salts, vitamin B ₆ and its derivatives and their salts, vitamin B ₁₂ and its derivatives and their salts , vitamin C and its derivatives and their salts, vitamin D and its derivatives and their salts, vitamin E and its derivatives and their salts, hesperidin and its derivatives and their salts, etc.) Glycyrrhiza, licorice, bellflower, peony, senega, etc., ingredients listed in the 17th revision of the Japanese Pharmacopoeia, Articles of Pharmaceuticals, "Crude drugs, etc."), and the like. These physiologically active ingredients may be used singly or in combination of two or more.

Examples of additives include binders, excipients, disintegrants, lubricants, flavors, pigments, base materials, sweeteners, acidulants and the like.
Binders include sucrose, gelatin, gum arabic powder, polyvinylpyrrolidone, pullulan, dextrin and the like. Excipients include crystalline cellulose, lactose (hydrate), corn starch, powdered sugar, mannitol, L-cysteine and the like.
Disintegrants include low-substituted hydroxypropyl cellulose, crospovidone, croscarmellose sodium and the like.
Lubricants include magnesium stearate, sodium stearyl fumarate, sucrose fatty acid ester, light anhydrous silicic acid and the like. Examples of fragrances include menthol, limonene, and plant essential oils (mint oil, mint oil, lychee oil, orange oil, lemon oil, etc.).
Pigments include iron sesquioxide and the like. Water, ethanol, etc. are mentioned as a base material. Sweeteners include saccharin sodium, aspartame, stevia, dipotassium glycyrrhizinate, acesulfame potassium, thaumatin, sucralose and the like.
Acidulants include citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, lactic acid and salts thereof. These additives may be used singly or in combination of two or more.

The sum of components (A) to (B) and optional components does not exceed 100% by mass.

Dosage forms for solid pharmaceutical formulations include oral administration. Solid pharmaceutical preparations for oral administration include tablets, capsules, pills, granules, powders, fine granules and the like. Examples of tablets include uncoated tablets, coated tablets (film-coated tablets, sugar-coated tablets, etc.) and the like. Solid pharmaceutical preparations may also be orally disintegrating tablets, chewable tablets, effervescent tablets, and the like.

The size of the tablet is not particularly limited in terms of the effects of the present invention, but the diameter φ of the tablet is preferably 6 to 14 mm in terms of ease of handling and swallowability of the tablet.
The shape of the tablet is not particularly limited in terms of the effect of the present invention, but from the viewpoint of ease of handling and swallowing of the tablet, a shape having a cylindrical portion and a bulging portion that bulges vertically from the cylindrical portion is preferable. Examples of tablets having a shape having a cylindrical portion and a bulging portion include R tablets (standard R tablets, sugar-coated R tablets, etc.), two-step R tablets, Sumi square flat tablets, Sumi round flat tablets, and the like. Although the bulging portion of these tablets may be vertically asymmetrical, it is preferably vertically symmetrical.
The shapes of the standard R tablet, the sugar-coated R tablet, the two-tiered R tablet, the round sumi square flat tablet, and the round sumi round flat tablet will be described in detail below with reference to the drawings.

As shown in FIG. 1, the standard R tablet or sugar-coated R tablet 100 has a cylindrical portion 8, a first bulging portion 12, and a second bulging portion 22. The first bulging portion 12 , and second bulges 22 are biconvex tablets in which the radius of curvature R of the surface curve is constant regardless of the position of the bulge surface.
The first bulging portion 12 bulges from the vicinity of the periphery of one end face of the cylindrical portion 8 toward the center of the one end face. The second bulging portion 22 bulges from the vicinity of the periphery of the other end face of the cylindrical portion 8 toward the center of the other end face.
Here, the "curvature radius of the surface curve of the first bulging portion 12" means that the first bulging portion 12 is in a cross section taken in a direction perpendicular to the end surface of the cylindrical portion 8 so as to pass through the zenith 12A. It is the radius of a circle when the curve drawn by the surface of the bulging portion 12 is regarded as a part of the circle.
The “curvature radius of the surface curve of the second bulging portion 22” refers to the second bulging portion in a cross section taken in a direction perpendicular to the end surface of the cylindrical portion 8 so as to pass through the zenith 22A. It is the radius of the circle when the curve drawn by the surface of 22 is regarded as a part of the circle.
The zenith 12A of the first bulging portion 12 is the highest point with respect to one end face. The zenith 22A of the second bulging portion 22 is the lowest point with respect to the other end face.
The curvature radius R of the first bulging portion 12 and the curvature radius R of the second bulging portion 22 may be the same or different, and are preferably the same from the viewpoint of tablet strength.

As shown in FIG. 2, the two-stage R lock 200 has a columnar portion 8, a first bulging portion 12, and a second bulging portion 22. The first bulging portion 12, the second The curvature radius R1 of the rising portion from the peripheral edge of each bulging portion 22 and the curvature radius R2 of the zenith 12A are different, and R1<R2.
Here, the "curvature radius of the surface curve of the first bulging portion 12" and the "curvature radius of the surface curve of the first bulging portion 22" are the same as those of the standard R tablet or the sugar-coated R tablet 100. .
The radius of curvature R1 of the first bulging portion 12 and the radius of curvature R1 of the second bulging portion 22 may be the same or different. preferable.
The curvature radius R2 of the first bulging portion 12 and the curvature radius R2 of the second bulging portion 22 may be the same or different, and from the viewpoint of tablet strength, it is preferable that they are the same. preferable.

As shown in FIG. 3 , the round square flat tablet 300 is a biconvex tablet having a cylindrical portion 8 , a first bulging portion 12 and a second bulging portion 22 .
The first bulging portion 12 rises linearly at a predetermined rising angle θ from the vicinity of the peripheral edge of one end face of the cylindrical portion 8 toward the center of the one end face, and any region including the zenith 12A is flat. becomes.
The second bulging portion 22 rises linearly at a predetermined rising angle θ toward the center of the other end face from the vicinity of the peripheral edge of the other end face of the cylindrical portion 8, and any region including the zenith 22A is flat. becomes.
The rising angle θ of the first bulging portion 12 and the rising angle θ of the second bulging portion 22 may be the same or different, and should be the same from the viewpoint of tablet strength. is preferred.

As shown in FIG. 4 , the round round flat tablet 400 is a biconvex tablet having a cylindrical portion 8 , a first bulging portion 12 and a second bulging portion 22 .
The first bulging portion 12 rises from the vicinity of the peripheral edge of one end face of the cylindrical portion 8 toward the center of the one end face with a predetermined R, and any region including the zenith 12A is flat.
The second bulging portion 22 rises from the vicinity of the peripheral edge of the other end face of the cylindrical portion 8 toward the center of the other end face with a predetermined R, and any region including the zenith 22A is flat.
The curvature radius R of the first bulging portion 12 and the curvature radius R of the second bulging portion 22 may be the same or different, and from the viewpoint of tablet strength, they should be the same. preferable.

As shown in FIGS. 1 to 4, the standard R tablet or sugar-coated R tablet 100, the two-stage R tablet 200, the round corner flat tablet 300, and the round round flat tablet 400 each have a It has a horizontal surface (land portion 14 ) that is annular in plan view, and has a horizontal surface (land portion 24 ) that is annular in plan view on the outer periphery of the second swelling portion 22 .
The width of the land portion 14 is W. The "width of the land portion 14" is the distance from the peripheral edge of the first bulging portion 12 to the peripheral edge of the end face.
The width of the land portion 24 may be the same as W, or may be different. The width of the land portion 24 is preferably the same as W from the viewpoint of tablet strength.

From the viewpoint of ease of administration, the tablet size is preferably within the following range.
・Standard R lock: R = 4.0 to 24.0 mm, land width W = 0.05 to 0.1 mm.
· Sugar-coated R tablet: R = 2.0 to 18.5 mm, land width W = 0.01 to 0.1 mm.
・Two-stage R lock: R1 = 1.2 to 8.0 mm, R2 = 4.5 to 33 mm, land width W = 0.05 to 0.1 mm.
・Round round flat tablet: R = 0.7 to 5.0 mm, land width W = 0.05 to 0.1 mm.
・Circular square flat tablet: rise angle θ=25 to 35°, land width W=0.05 to 0.1 mm.

However, the shape of the tablet is not limited to the above example. The tablet may, for example, have no land portion and the tablet peripheral edge portion and the bulging rising portion may be in contact with each other. When the shape of the tablet is a round square flat tablet or a round round flat tablet, any one of the arbitrary region including the zenith of the first bulging portion and the arbitrary region including the zenith of the second bulging portion is It does not have to be flat. The shape of the tablet may not be circular in plan view, but may be elliptical in plan view, square in plan view, or a combination of circular and square in plan view.
Tablets may or may not be imprinted.

According to the 17th revision of the Japanese Pharmacopoeia, the friability of tablets is preferably 1.0% by mass or less. However, for the reasons described later, the friability of the tablet in the present invention is preferably 0.5% by mass or less, more preferably 0.3% by mass or less, further preferably 0.2% by mass or less, and 0.1% by mass. The following are particularly preferred. If the friability is equal to or less than the above upper limit, even if it is packed in a PTP (Press Through Pack) package and carried around, damage or the like is unlikely to occur. The tablet friability in the present invention is determined according to the tablet friability test described in the 17th revision of the Japanese Pharmacopoeia.

(Production method)
The production method of the solid pharmaceutical preparation is not particularly limited, and it can be produced by a known production method. For example, component (A), component (B) and, if necessary, other components are powder-mixed to obtain a mixture. When obtaining tablets (uncoated tablets, coated tablets), the obtained mixture is formed into uncoated tablets by a tableting machine, and coated as necessary to produce tablets. Preferably, component (A) is co-mixed with component (B). As a result, the components (A) and (B) can be easily dispersed uniformly in the mixture, and the number of times of mixing can be reduced and the mixing time can be shortened. Uniform mixing of the powders eliminates the need to increase the number of manufacturing steps, thereby reducing production costs. The preferred ratio of the components (A) and (B) when they are co-mixed is the same as the preferred ratio for suppressing moisture absorption.

As described above, according to the solid pharmaceutical composition of the present invention, since it contains components (A) and (B), it is possible to suppress moisture absorption. Therefore, the solid pharmaceutical preparation of the present invention is intended to suppress moisture absorption, and has improved dispersibility and disintegration properties.

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

(Raw materials used)
<(A) Component>
a1-1: Dried aluminum hydroxide gel (AL gel, trade name: S-100, standard: Japanese Pharmacopoeia, manufactured by Kyowa Chemical Industry Co., Ltd.).
a1-2: Glycine (trade name: glycine, standard: Japanese Pharmacopoeia, manufactured by Wako Pure Chemical Industries, Ltd.).
a2: Magnesium oxide (MgO, trade name: JP Magnesium Oxide Heavy, standard: JP, manufactured by Kyowa Chemical Industry Co., Ltd.).
a3: Magnesium aluminometasilicate (ALMg metasilicate, trade name: Neusilin, standard: official regulations, Fuji Chemical Industry Co., Ltd.).
a4: Synthetic aluminum silicate (synthetic silicate AL, trade name: synthetic aluminum silicate, standard: external regulations, manufactured by Kyowa Chemical Industry Co., Ltd.).
a5: Dihydroxyaluminum acetic acid (dihydroxy AL acetic acid, trade name: Glycinal, standard: external regulations, manufactured by Kyowa Chemical Industry Co., Ltd.).
a6: Synthetic hydrotalcite (synthetic HT, trade name: Alkamac SN, standard: external regulations, manufactured by Kyowa Chemical Industry Co., Ltd.).
a8: Ranitidine hydrochloride (trade name: ranitidine hydrochloride, specifications: external regulations, manufactured by Jiang Suo Han Sutong Pharmaceutical Co., Ltd.).
a10: Sucralfate (trade name: sucralfate hydrate, standard: external regulations, manufactured by Fuji Chemical Industry Co., Ltd.).

<(B) Component>
b1: meloxicam (trade name: meloxicam, manufactured by SUN Pharma).

<Optional component>
Corn starch: (corn starch, manufactured by Matsutani Chemical Industry Co., Ltd.).
Magnesium stearate: (Mg stearate, manufactured by Taihei Kagaku Sangyo Co., Ltd.).
Lactose: (Pharmatose 200M (trade name), manufactured by DMV).

(Examples 1-9)
Based on the compositions (unit: parts by mass) shown in Tables 1 to 4, the components (A) to (B) were powder-mixed in a polyethylene bag to obtain 200 g of mixed powder.
5 g of the mixed powder of each example was placed in a glass screw cap bottle (SV-50A) to prepare a measurement sample.
The measurement sample was stored in a constant temperature and humidity chamber at 40° C. and 75% RH for 3 days without covering the screw cap bottle. The mass before and after storage was measured, and the difference was taken as the moisture absorption amount (g). Based on the obtained moisture absorption amount, the moisture absorption inhibition rate Q was determined by the following formula (s). The results are shown in the table.

Moisture absorption suppression rate Q (%) = (NM) / N x 100 (s)

In the formula (s), N is the moisture absorption amount (g) per 1 g of component (A) in the formulation excluding component (B). M is the moisture absorption amount (g) per 1 g of component (A) in each example. For example, when calculating the moisture absorption suppression rate of Examples 1-1 to 1-3, N is the moisture absorption amount (g) per 1 g of component (A) in Comparative Example 1, and M is Examples 1-1 to 1-1. It is the moisture absorption amount (g) per 1 g of component (A) in -3.

As shown in Tables 1 to 4, each of Examples 1 to 9 had a moisture absorption suppression rate of 25 to 100%.
From the above results, it was confirmed that the hygroscopicity of solid pharmaceutical formulations can be suppressed by applying the present invention.
However, Examples 1-1 to 1-3, 2, 4-1 to 4-2, 5, 8 and 9 are reference examples.

(Example 11)
Based on the composition (unit: parts by mass) shown in Table 5, components (A) to (B) and optional components were powder-mixed in a polyethylene bag to obtain 3 kg of mixed powder.
Using a rotary tableting machine (VIRG-2L, manufactured by Kikusui Seisakusho), the obtained mixed powder was compressed with a punch diameter of φ8 mm, R1 = 1.9 mm, R2 = 25.35 mm, W = 0.1 mm, and a tableting pressure of 3 kN. Tablets (two-tiered R tablets) of each example were obtained.
A 5 g tablet of each example was placed in a glass screw-capped bottle (SV-50A) and used as a measurement sample.
The measurement sample was stored in a constant temperature and humidity chamber at 40° C. and 75% RH for 3 days without covering the screw cap bottle. The mass before and after storage was measured, and the difference was taken as the moisture absorption amount (g). Based on the determined moisture absorption amount, the moisture absorption inhibition rate Q was determined by the above formula (s). The results are shown in the table.
Incidentally, N in the formula (s) is the moisture absorption amount (g) per 1 g of component (A) in the formulation without component (B), and M is the moisture absorption per 1 g of component (A) in each example. amount (g).

As shown in Table 5, Examples 11-1 and 11-2 to which the present invention was applied had moisture absorption suppression rates of 45 to 50%.
From the above results, it was confirmed that the hygroscopicity of solid pharmaceutical formulations can be suppressed by applying the present invention.
However, Examples 11-1 and 11-2 are reference examples.

(Example 20)
Tablets of each example were obtained in the same manner as in Example 11 based on the composition (unit: parts by mass) shown in Table 6. The moisture absorption inhibition rate of the obtained tablets was measured in the same manner as in Example 11, and the results are shown in the table. In addition, the tablet of each example was measured for friability (% by mass) in accordance with the Japanese Pharmacopoeia 17th Edition "Tablet friability test method", and the results are shown in the table.

As shown in Table 6, the moisture absorption suppression rate of Examples 20-1 to 20-5 to which the present invention is applied is 26
~54%. From the above results, it was confirmed that the hygroscopicity of solid pharmaceutical formulations can be suppressed by applying the present invention.
Further, the friability of Examples 20-1 to 20-5 was 0.05 to 0.4% by mass.
However, Examples 20-1 to 20-5 are reference examples.

Claims (5)

containing (A) a disease-treating component (A) for both or one of the digestive organs and the digestive system, and (B) at least one drug selected from meloxicam and its pharmaceutically acceptable salts,
The component (A) is magnesium oxide (a2),
A solid pharmaceutical preparation, wherein the mass ratio represented by component (B)/component (a2) is 0.17 to 0.4. containing (A) a disease-treating component (A) for both or one of the digestive organs and the digestive system, and (B) at least one drug selected from meloxicam and its pharmaceutically acceptable salts,
The component (A) is dihydroxyaluminum aminoacetic acid (a5),
A solid pharmaceutical preparation, wherein the mass ratio represented by component (B)/component (a5) is 0.083 to 0.33. containing (A) a disease-treating component (A) for both or one of the digestive organs and the digestive system, and (B) at least one drug selected from meloxicam and its pharmaceutically acceptable salts,
The component (A) is a synthetic hydrotalcite (a6),
A solid pharmaceutical preparation, wherein the mass ratio represented by component (B)/component (a6) is 0.0025 to 0.1. The solid pharmaceutical formulation according to any one of claims 1 to 3 , which is a tablet, capsule, pill, granule, powder or fine granule. The solid pharmaceutical preparation according to any one of claims 1 to 4 , wherein the content of component (B) is 1 to 25% by mass.

Images