JP2002029964A - Solid pharmaceutical composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solid medicine composition which can reduce an unpleasant touch in mouth, can more quickly exhibit an antacid effect, and can thereby more surely exhibit a flavoring effect, when taken, than those of conventional solid medicine compositions, without passing through a complicated process. SOLUTION: This solid medicine composition for being disintegrated and/or dissolved in month, characterized by containing a physiologically active ingredient and an antacid and containing particles having particle diameters of <=30 μm in an amount of 90 wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a solid pharmaceutical composition which disintegrates and dissolves in the oral cavity. The present invention also relates to a method for producing such a solid pharmaceutical composition. More specifically, the present invention relates to a solid preparation that can have moderate hardness and has improved discomfort inherent to antacid-containing solid pharmaceutical compositions such as roughness and unpleasant taste upon taking.

[0002]

2. Description of the Related Art When a bioactive ingredient is used as a solid pharmaceutical composition, the unpleasant taste peculiar to the bioactive ingredient often deteriorates the ingestibility of the composition. Particularly for children, when a physiologically active ingredient having an unpleasant taste such as bitterness, sourness or astringency is incorporated, there are problems such as refusal of dosing and the necessity of taking with a large amount of water. As a solid pharmaceutical composition for internal use, a physiologically active ingredient and an excipient are preliminarily mixed or appropriately granulated, and then a granule is obtained, or a binder, a disintegrant, a disintegration aid, an excipient, A lubricant is added and the mixture is compressed and formed into tablets. In addition, it has been desired to reduce the amount of various additives from the viewpoint of ensuring portability and safety of commonly used solid pharmaceutical compositions. thereby exhibit as well as solid pharmaceutical composition is desired depressed until such a usability and 嗜 eosinophilic.

[0003] In response to these demands, a method of coating the surface of a physiologically active ingredient to suppress dissolution of the physiologically active ingredient in the mouth and reduce unpleasant taste is disclosed in Japanese Patent Publication No. 64-5004 and Japanese Patent Laid-Open Publication No. Sho 63-63.
301815 and JP-A-61-152623.
The release of the active ingredient in the living body may vary, and there is a problem in application to a solid pharmaceutical composition that requires precise dissolution performance, a complicated process is required for preparing these, or an organic solvent is used. There was a problem that it had to be used. Further, the effect of the addition of JP-A-2-25428 or the like, in which masking is performed by the addition of magnesium sulfate, cannot be expected to provide a sufficient flavoring effect even in a small amount.
Also, a method of clathrate has been devised as in JP-A-61-69729, but when the blending amount of the active ingredient is large, a larger amount of cyclodextrin, which is a host component relative to the active ingredient, is required. This leads to an increase in the total amount of the solid pharmaceutical composition, which leads to worsening of ingestibility. Further, there still remains a fundamental problem such as a delay in the elution rate of the included active ingredient, and it is considered that there is a serious problem particularly for an active ingredient which requires a quick effect. In recent years, it is widely known that antipyretics, analgesics, cold medicines and the like are formulated into tablets and granules and antacids are used, but in order to give desirable physical properties, starch, lactose, mannitol, etc. , And disintegrants such as carboxymethylcellulose and crystalline cellulose are mixed and added. Particularly, in the case of a solid pharmaceutical composition having a fast disintegration property in the oral cavity such as a chewable preparation, the taste of the active ingredient is directly spread in the mouth. Therefore, for example, a sweetener is often added to reduce bitterness. In this case, the physiologically active component having an unpleasant taste and the sweetener component are in different systems, and thus have different dissolution behaviors, so that a sufficient flavoring effect may not be exhibited. Sucrose is most commonly used as a sweetener, but in addition, mannitol,
Sugars such as fructose, dipotassium glycyrrhizinate, and saccharin, sodium saccharin, aspartame and the like as synthetic sweeteners are incorporated. The effects of increasing amounts of sucrose, mannitol, fructose, xylitol, glucose, etc. are insufficient, and increasing the amount may increase bitterness like aspartame, didipotassium glycyrrhizinate, saccharin and saccharin sodium. is there. In any case, these methods were devised as countermeasures from the taste, and were not sufficient methods for fundamentally eliminating the roughness and odor peculiar to antacids.

[0004]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above circumstances, and can reduce an unpleasant feeling in a mouth without performing complicated steps, and can exhibit an antacid effect more quickly. Therefore, it is an object of the present invention to provide a solid pharmaceutical composition that is more reliable in the flavoring effect when taken.

[0005]

Means for Solving the Problems The present inventor has proposed a solid pharmaceutical composition containing a physiologically active ingredient and an antacid, such as an unpleasant odor or roughness peculiar to the antacid when the composition disintegrates in the mouth. The present inventors have found that an unpleasant touch can be solved by setting the particle size of the antacid to 30 μm or less, and completed the present invention. That is, the present invention provides a solid pharmaceutical composition for disintegrating and / or dissolving in the mouth, comprising a physiologically active ingredient and an antacid, wherein 90% by mass or more has a particle size of 30 μm or less. I do. Further, the present invention relates to 90 to 1
Antacid layer component particles containing antacid particles having a particle diameter of 30% by mass or less and an average particle diameter of 1 to 20 μm, and an average of 0.5 to 2 times the antacid average particle diameter. Provided is a method for producing a multilayer solid pharmaceutical composition, which comprises compression-molding bioactive ingredient layer particles containing poorly water-soluble bioactive ingredient particles having a particle size.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION As a physiologically active ingredient, for example, fursultiamine, ranitidine hydrochloride, cimetidine, naproxen, diclofenac sodium, piroxicam,
Famotidine, azulene, indomethacin, salicylic acid, aspirin, ketoprofen, ibuprofen, isosorbide dinitrate, dihydrocodeine phosphate, ephedrine, ephedrine hydrochloride, phenylpropanolamine hydrochloride, chlorpheniramine maleate, acetaminophen, theophylline, caffeine, anhydrous caffeine, Various vitamins such as cephalexin, ampicillin, sulfixazole, sucralfate, riboflavin and ascorbic acid, minerals, amino acids, peptides and proteins (eg, insulin, vasopressin, interferon, urokinase, serratiopeptidase, somatostatin) and the like. Can be In the present invention, the shape, particle size and the like of the physiologically active ingredient are not particularly limited, but it is preferable to match the particle size with the particles containing the antacid. Specifically, the average particle size of the physiologically active component is preferably 0.5 to 2 times, more preferably 0.8 to 1.5 times the average particle size of the antacid described below. The physiologically active ingredient may be a mixture of physiologically active ingredient particles of preferably 1 to 30 μm, more preferably 1 to 20 μm as they are, or may be granulated particles mixed with other optional components such as an excipient. It is also preferable to coat with a water-soluble polymer compound. When blended as granulated granules or fine granules, usually granulate with excipients, etc., 1-3
It is preferable to form granulated particles of about 00 μm. In particular, since a fibrous material requires a long time, it is preferable to carry out a pretreatment by itself in advance to obtain the above-mentioned particle diameter, and then to carry out a treatment for homogenization. The content of the physiologically active ingredient in the solid pharmaceutical composition of the present invention is preferably 20 to 90%, more preferably 25 to 50%, based on the total mass of the solid pharmaceutical composition.

In the case of granulating the physiologically active ingredient in the present invention, any of a wet method and a dry method can be used as long as the stability is not impaired. Typical methods include roll compression, spray granulation, stirring granulation,
Rolling granulation and the like. Alternatively, after mixing the physiologically active ingredient and an appropriate additive with a kneader or a ribbon mixer, adding a binder, the mixture may be kneaded, dried and sized to use. In this case, a mechanism to rotate a disk with a pendulum-shaped hammer to match the particle diameter of the antacid, a mechanism to grind the particles by shear force,
Alternatively, it is more preferable to use a method in which suspended particles collide with each other at a high speed in a gas circulating at a high speed. In this case, examples of commercially available devices include a turbo mill (Turbo Kogyo), a sample mill (Fuji Paudal), and a jet mill (Freund Co., Ltd.).

As the antacid in the present invention, aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, aluminum hydroxide gel, dried aluminum hydroxide, hydroxide Aluminum / magnesium carbonate mixed dry gel, co-precipitated product of aluminum hydroxide / sodium bicarbonate, aluminum hydroxide /
It can be selected from one or more components selected from a coprecipitation product of calcium carbonate / magnesium carbonate, a coprecipitation product of aluminum hydroxide / potassium aluminum sulfate, magnesium carbonate, calcium carbonate, and magnesium aluminate metasilicate. Among them, magnesium oxide, synthetic hydrotalcite, aluminum glycinate, magnesium carbonate, calcium carbonate are preferred, magnesium carbonate,
Almium glycinate and magnesium oxide are more preferred.

The particle size of the antacid used in the present invention is 90% by mass or more, for example, 90 to 100% by mass, preferably 95 to 100% by mass of the antacid, 30 μm or less, preferably 1 to 30 μm, Preferably it is 1 to 20 μm, most preferably 1 to 10 μm. The average particle size is preferably from 1 to 20 μm, particularly preferably from 3 to 10 μm. The antacid can be used by collecting fractions having a particle diameter of 30 μm or less. Preferred antacid particles have a specific surface area of 10,000 cm ² / g or more and have a high effect of eliminating unpleasant roughness. More preferably, 20
000 cm ² / g or more, particularly preferred is 30,000 c
m ² / g or more. The antacid particles having a high specific surface area can be obtained by a spray drying method. The content of the antacid in the solid pharmaceutical composition of the present invention is preferably 10 to 70% based on the total mass of the solid pharmaceutical composition,
More preferably, it is 20 to 50%. Further, the antacid particles are preferably coated with a water-soluble polymer compound such as hydroxypropylcellulose, carmellose, or polyvinylpyrrolidone. The antacid particles of the present invention can mask not only discomfort such as roughness in the mouth but also unpleasant scents.

[0010] As an ingredient for correcting the unpleasant taste of the antacid, a component having sweetness, sourness, and umami can be added.
The use of components that act on the taste receptor is generally used, but when used in combination with these methods, the above-mentioned specific surface area and particle conditions are also suitable for uniform masking. The components having a sweetness that can be used in combination with the present invention include saccharin, fructose, glucose, lactose, reduced maltose, saccharin, sodium saccharin,
Aspartame, natural products include glycyrrhizic acid, dipotassium glycyrrhizinate, amalty, and sugar alcohols include lactitol, maltitol, sorbitol, erythritol and the like. Ascorbic acid, tartaric acid, malic acid, citric acid, etc. can be used as components having a sour taste.Inosinic acid, sodium glutamate, etc. can be used as components having a umami taste. . Further, a plurality of these may be blended and used.

The amount of the component that corrects the unpleasant taste varies depending on the solubility of the component having an unpleasant taste in water and the degree of the taste, but it is 0.1% based on the total content of the physiologically active component and the antacid. The content is preferably about 1 to 150% by mass.

In preparing this composition, if necessary, disintegrating agents such as cellulose and its derivatives, starch and its derivatives, hydroxypropylcellulose (substitution degree: 53.4 to 77.5%), methylcellulose, gelatin , Vinylpyrrolidone, binders such as partially pregelatinized starch,
Dyes and the like can be appropriately added as long as the effects of the present invention are not hindered.

The granulation when other additives are blended with the antacid is a known granulation method such as melt extrusion granulation, tumbling granulation, fluidized bed granulation or roll compression granulation. Can be used. In this case, when granulating or compressing, the composition of the present invention, if necessary, usually used additives such as lubricants, binders, coating agents, excipients,
Disintegrants, disintegration aids, etc. can be used alone or in combination of two or more. Specific examples of the optional additive include the following components. In addition, these additives can be appropriately added within a range that does not impair the effects of the present invention.

Lubricants: gum arabic, cacao butter, carnauba wax, hydrous silicon dioxide, dried aluminum hydroxide gel, glycerin, magnesium silicate, liquid paraffin, crystalline cellulose, sucrose fatty acid ester, stearyl alcohol, stearic acid, gelatin, Lactose, white sugar,
Hydroxypropylcellulose, hydroxypropylmethylcellulose, fumaric acid, beeswax and the like. Among these lubricants more preferable lubricants that can eliminate roughness are cocoa butter, stearyl alcohol, hydrogenated castor oil,
Beeswax and talc are preferred. Particularly, talc and hydrogenated castor oil are preferred.

Binder: hydroxypropylcellulose (degree of substitution: 53.4-77.5%), methylcellulose, gelatin, polyvinylpyrrolidone, partially pregelatinized starch and the like. Coating agents: glycerin, liquid paraffin, silicone resin, stearic acid, gelatin, sorbitol, corn oil, lactose, polyvinyl alcohol, macrogol, methacrylic acid copolymer, calcium hydrogen phosphate, sodium hydrogen phosphate and the like. Excipients: gum arabic, ethyl cellulose, kaolin,
Cocoa butter, fructose, silicon dioxide, xylitol, citric acid or its salts, crystalline cellulose, stearic acid or its salts, dextran, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, macrogol, calcium hydrogen phosphate, sodium hydrogen phosphate etc. Disintegrant: cellulose or a derivative thereof, starch or a derivative thereof, and the like. Disintegration aid: cellulose or a derivative thereof, stearic acid,
Sodium hydrogen carbonate, hydroxypropyl cellulose and the like. Food additives: thiamine mononitrate, riboflavin, pyridoxine hydrochloride, ascorbic acid, vitamin B _12, folic acid, calcium pantothenate, potassium chloride,蠣殻end, niacinamide, biotin, seaweed powder, nicotinamide, cyanocobalamin, precipitated calcium carbonate, In addition to magnesium carbonate, brewer's yeast, spring chrysanthemum, butterbur, shimeji, spinach-derived plant fiber, supplements (tablets, jellies, bars,
Flakes, granules).

The form of the solid pharmaceutical composition of the present invention is not particularly limited. For example, the solid pharmaceutical composition is manufactured as tablets, capsules, sachets, oral tablets, chewable tablets, troche tablets, buccal tablets and the like. be able to. In the present invention, the antacid layer component particles containing the antacid particles and the bioactive component layer particles containing the bioactive component particles are compression-molded to form a multilayer solid pharmaceutical composition. Can be. The compression molding method in such a production method is not particularly limited, and may be performed by, for example, any of a wet or dry indirect compression method and a direct compression method. At the time of compression molding, the tableting pressure is preferably 0.5 to 3 t, whereby the hardness is 5 to 15 kgf, more preferably 2 to 10 kf.
gf tablets. Incidentally, when the solid pharmaceutical composition of the present invention is a tablet, it may be in various forms, a circular tablet whose form when viewed from the top is a perfect circle, or
It may be a modified tablet having an elliptical diameter, a triangle, a square, a hexagon, a lens, a disk, or the like. The size of such a tablet is not particularly limited, and may be, for example, 5 to 20 mm in diameter.

[0017]

According to the present invention, it is possible to improve the characteristic unpleasant smell and rough feel of an antacid without taking complicated steps, and to improve the ingestibility of a solid pharmaceutical composition. is there. In addition, p by an antacid contained in the composition
The rate of increase of H is fast, that is, the effect of the antacid is obtained faster. Hereinafter, the present invention will be described specifically with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples.

[0018]

EXAMPLE 1 Aspirin (average particle size: 5μ) was selected as a physiologically active ingredient, 2,000 g of the substance was weighed, 200 g of corn starch was added, and the mixture was mixed for 5 minutes with a V-type mixer (V-5: Tokuju Kosakusho). After that, the mixture was roll-compressed with an ALEXANDERWERK EINSPEIS type, and sized to obtain granules suitable for the Japanese granules. Next, select magnesium carbonate produced by the spray drying method as an antacid,
This was pulverized with a jet pulverizer (TJ60: manufactured by Turbo Kogyo). The average particle size was 5 μm (2 to 10 μm was 100%), and the specific surface area was 15000 m ² / g. 300 g of the solution was placed in a fluidized bed granulator (FLO-MINI: manufactured by Freund), and 100 g of a solution prepared by previously dissolving 60 g of hydroxypropyl cellulose in 940 g of water was sprayed at 70 ° C. In addition, partially pregelatinized starch 30
g was added and mixed with a V-type mixer (V-5: manufactured by Tokuju Seisakusho) for 5 minutes. Next, 10 g of talc was added and mixed for 3 minutes. Next, aspirin granules were made into a first layer and antacid granules were made into a second layer using a rotary tableting machine (12HUK: manufactured by Kikusui Seisakusho) to obtain round tablets having a diameter of 8 mm and a weight of 393 mg. (Tabletting pressure: 1t, hardness: 9.1kgf) A preparation (comparative example) using magnesium carbonate of 50 to 150 μm was prepared by the same production method as described above, and a sensory test was performed to evaluate the feeling during mastication by six panels. +: There is a very rough feel ±: Slightly rough feel-: Little rough feel is felt Table 1 All the subjects felt the roughness of the tablet of the comparative example 15 seconds after putting it in the mouth, and none of the examples felt such roughness.

Example 2 (1) Ibuprofen (average particle size: 5 μm) was selected as a physiologically active ingredient, 1500 g thereof was weighed, and 400 g of crystalline cellulose was added to the mixture to form a V-type mixer (V-5: Tokuju Kosakusho) )
After mixing for 5 minutes, the mixture was roll-compressed with an ALEXANDERWERK EINSPEIS type, and sized to obtain granules compatible with JP granules. (2) Precipitated calcium carbonate was selected as an antacid, and this was pulverized by a jet pulverizer (TJ60: manufactured by Turbo Kogyo). The average particle size was 8 μm (100% of 5 to 12 μm).
300 g of this was placed in a fluidized bed granulator (FLO-MINI: manufactured by Freund), and 70 g of hydroxypropyl cellulose was previously added at 70 ° C.
Was dissolved in 940 g of water and sprayed with 100 g. Further, 30 g of carmellose was added thereto, and the mixture was mixed with a V-type mixer (V-5: manufactured by Tokuju Seisakusho) for 5 minutes. Next, 10 g of talc was added and mixed for 3 minutes. (1) and (2) are tableted in two layers with a rotary tableting machine (12HUK: manufactured by Kikusui Seisakusho) and the diameter is 8m.
m, a round tablet weighing 268 mg. (Tabletting pressure: 1.1t,
Hardness: 8.6kgf) A preparation (comparative example) using precipitated calcium carbonate of 40 to 80 μm was prepared by the same production method as described above, and evaluated by performing a sensory test of tablets in the mouth by a panel of six persons. +: There is a very rough feeling ±: Slight roughness is felt −: Little roughness is felt Table 2 All the subjects felt the roughness of the tablet of the comparative example 15 seconds after putting it in the mouth, and none of the examples felt such roughness.

Example 3 (1) Aspirin was selected as a physiologically active ingredient,
Weigh 00 g and add low-substituted hydroxypropylcellulose
After adding 200 g and mixing with a V-type mixer (V-5: Tokushou Kogyo) for 5 minutes, the mixture was roll-compressed with an ALEXANDERWERK EINSPEIS type and sized to obtain granules compatible with the Japanese granules.
(2) Aluminum glycinate was selected as an antacid, and this was pulverized by a jet pulverizer (TJ60: manufactured by Turbo Kogyo). The average particle size was 8 μm (5 to 12 μm 100%). Put 300 g of this in a fluidized bed granulator (FLO-MINI: manufactured by Freund) at 70 ° C.
100 g of a solution of g of hydroxypropylcellulose in 900 g of water was sprayed. Further, 100 g of anhydrous caffeine, 60 g of allyl isopropylacetyl urea and 1 g of vitamin B ₂ were added as physiologically active ingredients, and 30 g of crystalline cellulose was further added, followed by mixing with a V-type mixer (V-5: manufactured by Tokuju Seisakusho) for 5 minutes. did. Next, 10 g of talc was added and mixed for 3 minutes. Each of (1) and (2) was tableted in two layers with a rotary tableting machine (L-41: manufactured by Hata Iron Works) to obtain round tablets having a diameter of 11 mm and a weight of 475.5 mg. (Tabletting pressure: 1.5t, hardness: 12.3kgf) A preparation (comparative example) using aluminum glycinate of 50 to 150 μm was prepared by the same production method as described above,
Sensory testing of the tablet in the mouth by a panel of six persons was performed and evaluated. +: There is a very rough feel ±: Slightly rough feel-: Little rough feel is felt Table 3 All the subjects felt the roughness of the tablet of the comparative example 15 seconds after putting it in the mouth, and none of the examples felt such roughness.

Example 4 Ethenzamide was selected as a physiologically active ingredient, and 2000 g of the same was selected.
Weigh the low-substituted hydroxypropylcellulose 600
g was added and mixed with a V-type mixer (V-5: Tokushou Kogyosho) for 5 minutes. Next, the magnesium oxide was pulverized with a jet pulverizer (TJ60 type: manufactured by Turbo Kogyo). This particle size is
It was 3 to 18 μm (specific surface area: 30,000 m ² / g, average particle size: 5 μm). 300 g of this was placed in a fluidized bed granulator (FLO-MINI: manufactured by Freund), and 100 g of polyvinylpyrrolidone K was previously prepared at 70 ° C.
100 g of a solution of -30 in 900 g of water was sprayed. Further, 100 g of anhydrous caffeine and 60 g of allyl isopropylacetyl urea were added thereto as physiologically active ingredients, and 30 g of crystalline cellulose was further added, followed by mixing for 5 minutes with a V-type mixer (V-5: manufactured by Tokuju Seisakusho). Next, 5 g of magnesium stearate and 5 g of talc were added and mixed for 3 minutes. Next, tablets were produced using a rotary tableting machine (L-41: manufactured by Hata Iron Works) to obtain circular tablets having a diameter of 11 mm and a weight of mg. (Tabletting pressure: 1.3
t, hardness: 13.4kgf) A preparation (comparative example) using magnesium oxide of 50 to 150 μm was prepared by the same production method as described above, and evaluated by performing a sensory test of tablets in the mouth by a panel of six persons. +: There is a very rough feeling ±: Slight roughness is felt-: Little roughness is felt Table 4 All the subjects felt the roughness of the tablet of the comparative example 15 seconds after putting it in the mouth, and none of the examples clearly felt such roughness.

Example 5 Aspirin was selected as a physiologically active ingredient, 2000 g of the aspirin was weighed, and 600 g of low-substituted hydroxypropylcellulose was weighed.
Was added and mixed with a V-type mixer (V-5: Tokushou Kogyosho) for 5 minutes. Then, magnesium carbonate was jet-milled (TJ
(Model 60: manufactured by Turbo Kogyo). This particle size is 3-1
It was 8 μm. 300 g of this fluidized bed granulator (FLO-MINI:
100 g of gelatin beforehand at 70 ° C in a Freund's
100 g of a solution dissolved in 1 g of water were sprayed. Further, 100 g of acetaminophen and 6 g of aspartame were added as physiologically active components, and 30 g of crystalline cellulose was further added. The mixture was mixed for 5 minutes with a V-type mixer (V-5: manufactured by Tokuju Seisakusho). Next, 5 g of magnesium stearate and 5 g of hydrogenated castor oil were added and mixed for 3 minutes. Next, tablets were produced using a rotary tableting machine (L-41: manufactured by Hata Iron Works), with a diameter of 11 mm and a weight of 44.
8 mg round tablets were obtained. (Tabletting pressure: 1.4t, hardness: 10.1
kgf) A preparation (comparative example) using magnesium carbonate of 35 to 120 μm was prepared by the same production method as described above, and evaluated by performing a sensory test of tablets in the mouth by a panel of six persons. +: There is a very rough feel ±: Slightly rough feel-: Little rough feel is felt Table 5 All subjects felt the roughness of the tablet of the comparative example 5 seconds after putting it in the mouth, and none of the examples clearly felt such roughness. The tablets of Examples 1 to 5 had a hardness suitable for mastication, had no cracks due to vibration or the like, and had good strength. 150ml artificial gastric juice
(PH 1.5) It was recognized that the rate of increase in pH when one tablet was added was fast, and that the effect of the antacid was obtained quickly.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (reference) A61P 1/04 A61P 1/04 29/02 29/02 F term (reference) 4C076 AA32 AA49 BB02 BB22 CC01 CC16 DD28 EE31H EE32H EE38 FF06 FF52 4C084 AA20 ZA692 4C086 AA01 DA17 HA04 HA16 MA02 MA04 MA05 MA34 MA57 NA09 ZA08 ZA69

Claims (10)

[Claims] 1. A composition comprising a physiologically active ingredient and an antacid,
A solid pharmaceutical composition for disintegration and / or dissolution in the mouth, characterized in that not less than 30% by mass of the particles have a particle size of 30% by mass or less. 2. The antacid particles have a specific surface area of 10,000 cm.
^2. The solid pharmaceutical composition according to claim 1, which is not less than ² / g. 3. The solid pharmaceutical composition according to claim 1, wherein the antacid particles are particles coated with a water-soluble polymer compound. 4. The composition according to claim 1, further comprising a flavor component.
4. The solid pharmaceutical composition according to any one of 3. 5. The solid pharmaceutical composition according to claim 1, which is a compression-molded solid having a hardness of 5 to 15 kgf. 6. The solid pharmaceutical composition according to claim 1, which is a multilayer tablet having a layer containing antacid particles and a layer containing particles containing a physiologically active ingredient. 7. The solid pharmaceutical composition according to claim 1, which is a chewable tablet. 8. The solid pharmaceutical composition according to claim 1, which is a lozenge. 9. An antacid particle having an average particle diameter of 1 to 20 μm.
The solid pharmaceutical composition according to any one of claims 1 to 8, wherein the average particle size of the physiologically active ingredient is 0.5 to 2 times the average particle size of the antacid. 10. 90 to 100% by weight of a particle diameter of 30 μm
Antacid layer component particles containing antacid particles having an average particle diameter of 1 to 20 μm or less, and a poorly water-soluble physiology having an average particle diameter of 0.5 to 2 times the antacid average particle diameter. A method for producing a multilayer solid pharmaceutical composition, comprising compression-forming physiologically active ingredient layer particles containing active ingredient particles.