Pharmaceutical composition

Abstract

To provide a pharmaceutical composition that suppresses wetting and / or dissolution due to interaction when simultaneously blending diphenhydramine or a salt thereof dextromethorphan or a salt thereof and guaifenesin and also suppresses a degradation of appearance quality.SOLUTION: A pharmaceutical composition contains (a) diphenhydramine or a salt thereof, (b) dextromethorphan or a salt thereof and (c) guaifenesin, and (d) at least one selected from the group consisting of a silicate compound and magnesium stearate.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition containing diphenhydramine or a salt thereof.

Background Art

[0002] In pharmaceuticals, especially general pharmaceuticals such as cold remedies and analgesics, multiple medicinal ingredients are formulated. For example, in cold remedies, pharmaceuticals containing various medicinal ingredients such as antipyretics, antihistamines, antitussives, expectorants, and nasal medications are widely distributed. In such preparations containing multiple medicinal ingredients, interactions occur between the formulated medicinal ingredients, and physicochemical changes such as changes in properties are likely to occur.

[0003] As agents used as active ingredients in cold remedies, for example, diphenhydramine as an antihistamine, dextromethorphan as an antitussive, guaifenesin as an expectorant, etc. are known. Patent Document 1 discloses a stable pharmaceutical composition containing a pharmaceutical active ingredient and silicic acid-treated crystalline cellulose (silicated crystalline cellulose), and examples of the pharmaceutical active ingredient include dextromethorphan, guaifenesin, diphenhydramine, etc.

[0004] Further, Patent Document 2 discloses a cold remedy that contains naproxen or a salt thereof and a pharmaceutical ingredient selected from an anti-rhinitis action ingredient, an antitussive ingredient, and an expectorant ingredient as a cold remedy with an improved therapeutic and alleviating effect on various symptoms of a cold, and examples of the pharmaceutical ingredient include diphenhydramine, dextromethorphan, guaifenesin, etc. It is also described that the cold remedy may contain a silicate such as magnesium silicate, synthetic aluminum silicate, or magnesium aluminum aluminosilicate.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

[0006] Although any of the above documents shows that a plurality of active ingredients can be formulated in pharmaceuticals such as cold remedies, there is no description or suggestion at all regarding the problem that when (a) diphenhydramine or its salt, (b) dextromethorphan or its salt, and (c) guaifenesin are formulated simultaneously, wetting and / or dissolution are caused by the interaction of these drugs, deteriorating the appearance quality. An object of the present invention is to provide a pharmaceutical composition that suppresses wetting and / or dissolution due to the interaction when the above three components (a), (b), and (c) are formulated simultaneously and suppresses deterioration of the appearance quality. [Means for Solving the Problems]

[0007] As a result of intensive studies, the present inventors have found that by formulating at least one selected from the group consisting of (d) a silicic acid compound and magnesium stearate in addition to the above three components (a), (b), and (c), the above problems can be solved, and the present invention has been completed. That is, the present invention includes the following aspects. [1] A pharmaceutical composition comprising (a) diphenhydramine or its salt, (b) dextromethorphan or its salt, (c) guaifenesin, and at least one selected from the group consisting of (d) a silicic acid compound and magnesium stearate. [2] The pharmaceutical composition according to [1], wherein at least one selected from the group consisting of a silicic acid compound and magnesium stearate is 0.2 parts by mass or more with respect to 1 part by mass of (b) dextromethorphan or its salt. [3] The pharmaceutical composition according to [1] or [2], wherein at least one selected from the group consisting of a silicic acid compound and magnesium stearate is 0.2 parts by mass or more with respect to 1 part by mass of diphenhydramine or a salt thereof. [4] (c) The pharmaceutical composition according to any one of [1] to [3], wherein at least one selected from the group consisting of a silicic acid compound and magnesium stearate is 0.2 parts by mass or more with respect to 1 part by mass of guaifenesin. [5] The pharmaceutical composition according to any one of [1] to [4], wherein the content of at least one selected from the group consisting of a silicic acid compound and magnesium stearate is 0.05 to 50% by mass with respect to the whole composition. [6] (a) The pharmaceutical composition according to any one of [1] to [5], wherein diphenhydramine or a salt thereof is diphenhydramine hydrochloride. [7] (b) The pharmaceutical composition according to any one of [1] to [6], wherein dextromethorphan or a salt thereof is dextromethorphan hydrobromide hydrate. [8] (d) The pharmaceutical composition according to any one of [1] to [7], wherein the silicic acid compound is at least one selected from the group consisting of calcium silicate, light anhydrous silicic acid, hydrous silicon dioxide, magnesium aluminometasilicate, and silica. [9] The pharmaceutical composition according to any one of [1] to [8], which is used for colds.

[10] The pharmaceutical composition according to any one of [1] to [9], wherein the dosage form of the pharmaceutical composition is tablets, capsules, granules, powders or pills.

Advantages of the Invention

[0008] According to the present invention, in a pharmaceutical composition containing (a) diphenhydramine or a salt thereof, (b) dextromethorphan or a salt thereof, and (c) guaifenesin, by further incorporating at least one selected from the group consisting of (d) a silicic acid compound and magnesium stearate, wetting and / or dissolution due to the interaction of these drugs can be suppressed, and deterioration of the appearance quality can be suppressed. Therefore, according to the present invention, a pharmaceutical composition containing the above three components and having suppressed deterioration of the appearance quality can be provided.

Mode for Carrying Out the Invention

[0009] The pharmaceutical composition of the present invention is characterized by containing (a) diphenhydramine or a salt thereof, (b) dextromethorphan or a salt thereof, (c) guaifenesin, and at least one selected from the group consisting of (d) a silicic acid compound and magnesium stearate.

[0010] The "diphenhydramine or a salt thereof" in the present invention includes diphenhydramine and pharmaceutically acceptable salts thereof, as well as solvates of diphenhydramine and pharmaceutically acceptable salts thereof with water, alcohol, etc. Examples of diphenhydramine or a salt thereof include diphenhydramine, diphenhydramine hydrochloride, diphenhydramine citrate, diphenhydramine salicylate, diphenhydramine tannate, diphenhydramine lauryl sulfate, etc., and preferably diphenhydramine hydrochloride. These can be produced by known methods, and commercially available products can also be used. For example, diphenhydramine or a salt thereof conforming to the Japanese Pharmacopoeia can be used. The content of the "diphenhydramine or a salt thereof" contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately determined based on the above dosage, but for example, it is 0.1 to 20% by mass, preferably 0.5 to 10% by mass of the entire pharmaceutical composition.

[0011] "Dextromethorphan or a salt thereof" in the present invention includes dextromethorphan and its pharmaceutically acceptable salts, as well as solvates of dextromethorphan and its pharmaceutically acceptable salts with water, alcohol, etc. Examples of dextromethorphan or a salt thereof include dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthalein salt, etc., and preferably dextromethorphan hydrobromide hydrate. These can be produced by known methods, and commercially available products can also be used. For example, dextromethorphan or a salt thereof conforming to the Japanese Pharmacopoeia can be used. The content of "dextromethorphan or a salt thereof" contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately considered and determined based on the above dosage. For example, it is 0.1 to 5% by mass, preferably 0.5 to 3% by mass, of the whole pharmaceutical composition.

[0012] "Guaifenesin" in the present invention can be produced by known methods, and commercially available products can also be used. For example, guaifenesin conforming to the Japanese Pharmacopoeia can be used. The content of guaifenesin contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately considered and determined based on the above dosage. For example, it is 1 to 60% by mass, preferably 2.5 to 50% by mass, more preferably 5 to 30% by mass, of the whole pharmaceutical composition.

[0013] The "silicate compound" in the present invention is not particularly limited as long as the effects of the present invention are achieved. Examples thereof include known silicate compounds listed in the Japanese Pharmacopoeia, Pharmaceutical Additive Standards, Quasi-drug Raw Material Standards, and the like. Examples of the silicate compound include light anhydrous silicic acid, hydrous silicon dioxide, silica (e.g., wet silica, dry silica), metal silicate salts (e.g., aluminum silicate, calcium silicate, magnesium silicate), and metasilicate metal salts (e.g., magnesium aluminometasilicate, magnesium aluminometasilicate). Preferably, it is at least one selected from calcium silicate, light anhydrous silicic acid, hydrous silicon dioxide, magnesium aluminometasilicate, and silica. The content of the silicate compound contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately determined in consideration of the content of diphenhydramine or its salt, dextromethorphan or its salt, guaifenesin, and other medicinal components. For example, it is 0.01 to 70% by mass, preferably 0.05 to 50% by mass, more preferably 0.2 to 40% by mass of the whole pharmaceutical composition.

[0014] The "magnesium stearate" in the present invention can be produced by a known method, and commercially available products can also be used. For example, magnesium stearate conforming to the Japanese Pharmacopoeia can be used. The content of magnesium stearate contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately determined in consideration of the content of diphenhydramine or its salt, dextromethorphan or its salt, guaifenesin, and other medicinal components. For example, it is 10% by mass or less, preferably 7% by mass or less, more preferably 5% by mass or less of the whole pharmaceutical composition.

[0015] The mass ratio of (a) diphenhydramine or its salt and (d) a silicic acid compound and / or magnesium stearate contained in the pharmaceutical composition of the present invention is not particularly limited. For example, with respect to 1 part by mass of diphenhydramine or its salt, the silicic acid compound and / or magnesium stearate is, for example, 0.05 part by mass or more, preferably 0.2 part by mass or more, more preferably 0.5 part by mass or more as its lower limit, and 100 parts by mass or less, preferably 20 parts by mass or less as its upper limit.

[0016] The mass ratio of (b) dextromethorphan or its salt and (d) a silicic acid compound and / or magnesium stearate contained in the pharmaceutical composition of the present invention is not particularly limited. For example, with respect to 1 part by mass of dextromethorphan or its salt, the silicic acid compound and / or magnesium stearate is, for example, 0.05 part by mass or more, preferably 0.2 part by mass or more, more preferably 0.5 part by mass or more as its lower limit, and 100 parts by mass or less, preferably 20 parts by mass or less as its upper limit.

[0017] The mass ratio of (c) guaifenesin and (d) a silicic acid compound and / or magnesium stearate contained in the pharmaceutical composition of the present invention is not particularly limited. For example, with respect to 1 part by mass of guaifenesin, the silicic acid compound and / or magnesium stearate is, for example, 0.05 part by mass or more, preferably 0.1 part by mass or more, more preferably 0.2 part by mass or more as its lower limit, and 50 parts by mass or less, preferably 10 parts by mass or less as its upper limit.

[0018] The mass ratio of the combination of (a) diphenhydramine or its salt, (b) dextromethorphan or its salt and (c) guaifenesin and (d) a silicic acid compound and / or magnesium stearate contained in the pharmaceutical composition of the present invention is not particularly limited. For example, with respect to 1 part by mass of the above combination, the silicic acid compound and / or magnesium stearate is, for example, 0.05 part by mass or more, preferably 0.1 part by mass or more, more preferably 0.2 part by mass or more as its lower limit, and 50 parts by mass or less, preferably 10 parts by mass or less as its upper limit.

[0019] When diphenhydramine or its salt, dextromethorphan or its salt, and guaifenesin are formulated simultaneously, the wetting and / or dissolution and the resulting deterioration of the appearance quality are considered to be caused by the physical contact of the above three components. Therefore, as the pharmaceutical composition of the present invention, in particular, a pharmaceutical composition in which the above three components are not physically separated and are contained in a state where they can come into contact is exemplified. Such pharmaceutical compositions include, for example, tablets obtained by mixing and granulating these components in the same group and tableting, or tablets obtained by granulating these components in separate groups, then mixing the granulation powders and tableting.

[0020] In the pharmaceutical composition of the present invention, as long as the effects of the present invention are not inhibited, active ingredients other than the above active ingredients, for example, antipyretics, medications for rhinitis, antihistamines, antitussives, expectorants, bronchodilators, gastric mucosal protectants, vitamins, hypnotics and sedatives, mucolytic agents, anti-inflammatory agents, anticholinergics, crude drugs, traditional Chinese medicine prescriptions, etc. may be formulated.

[0021] Examples of antipyretics include aspirin (acetylsalicylic acid), aluminum aspirin, acetaminophen, ibuprofen, salicylamide, sodium salicylate, ethenzamide, salsalate, lactylphenetidine, ketoprofen, isopropylantipyrine, sodium loxoprofen, etc. Examples of medications for rhinitis include pseudoephedrine hydrochloride, chlorpheniramine dl - maleate, d - chlorpheniramine maleate, belladonna total alkaloids, isopropamide iodide, dipotassium glycyrrhizinate, etc. Examples of antihistamines include, for example, alimemazine tartrate, isothipendyl hydrochloride, promethazine methylene disalicylate, diphenylpyraline hydrochloride, diphenylpyraline theophyllinate, isothipendyl hydrochloride, difeterol hydrochloride, difeterol phosphate, triprolidine hydrochloride hydrate, tripelennamine hydrochloride, tonzylamine hydrochloride, phenergan hydrochloride, methdilazine hydrochloride, carbinoxamine diphenyldisulfonate, mebuphydroline napadisilate, carbinoxamine maleate, iproheptine hydrochloride, promethazine hydrochloride, carbinoxamine diphenyldisulfonate, alimemazine tartrate, phenergan tannate, promethazine methylene disalicylate, clemastine fumarate, mequitazine, etc. Examples of narcotic antitussives include, for example, codeine phosphate hydrate, dihydrocodeine phosphate, etc. Examples of non-narcotic antitussives include, for example, alokramide, isoaminyl, eprazinone, oxeladin, clofedanol, clobutinol, cloperastine, dibunate, dime morphine, tipepidine, noscapine, hydrocotarnine, pentoxyverine, benproperine, homoben, and their salts and hydrates. Examples of their salts and hydrates include, for example, alokramide hydrochloride, cloperastine hydrochloride, cloperastine fendizoate, sodium dibunate, dime morphine phosphate, tipepidine hibenzate, tipepidine citrate, pentoxyverine citrate, and their hydrates. Examples of expectorants include potassium guaiacolsulfonate, bromhexine hydrochloride, tipepidine citrate, L-carbocysteine, ammonium chloride, l-menthol, ammonia·wekiao essence, potassium cresolsulfonate, etc. Examples of bronchodilators include, for example, dl-methylephedrine hydrochloride, dl-methylephedrine saccharinate, trimethoquinol hydrochloride, phenylpropanolamine hydrochloride, methoxyphenamine hydrochloride, l-methylephedrine hydrochloride, pseudoephedrine hydrochloride, aminophylline, diprophylline, theophylline, proxiphylline, etc. Examples of gastric mucosa protective agents include glycine, aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, aluminum hydroxide gel, dried aluminum hydroxide gel, aluminum hydroxide / magnesium carbonate mixed dried gel, co-precipitation product of aluminum hydroxide / sodium bicarbonate, co-precipitation product of aluminum hydroxide / calcium carbonate / magnesium carbonate, co-precipitation product of magnesium hydroxide / aluminum potassium sulfate, and magnesium carbonate. Vitamins include, for example, vitamin B 1 Vitamin B 2 vitamin C or a derivative or a salt thereof; vitamin P (hesperidin) or a derivative or a salt thereof. Examples of hypnotic sedatives include allylisopropylacetylurea and bromvalerylurea. Examples of sputum dissolving agents include lysozyme chloride, L-ethylcysteine ​​hydrochloride, and methylcysteine ​​hydrochloride. Examples of anti-inflammatory agents include lysozyme chloride, serraptase, and glycyrrhizinic acid and its salts. Examples of anticholinergic agents include belladonna total alkaloids and isopropamide iodide. Examples of medicinal herbs include Ephedra, Nandina, Coptis Root, Onji, Licorice, Platycodon, Spiraea Root, Spiraea Root, Scutellaria, Senega, Fritillaria, Fennel, Phellodendron Bark, Coptis Rhizome, Zedoary, Chamomile, Cinnamon Bark, Gentiana Root, Bezoar, Animal Gall (including Yutang), Shajin, Ginger, Sophora Root, Clove, Tangerine Peel, Atractylodes Root, Jiru, Chikusetsuginjin, and Carrot. Examples of Chinese herbal prescriptions include Neto, Neto-ka-kikyo, Keipi-to, Koso-san, Saiko-keipi-to, Sho-saiko-to, Sho-sei-ryu-to, Bakumondo-to, Hange-kouboku-to, and Mao-to.

[0022] The pharmaceutical composition of the present invention is preferably caffeine-free. Examples of the caffeine compounds include caffeine, caffeine hydrate, anhydrous caffeine, pharmaceutically acceptable salts of caffeine (such as sodium benzoate caffeine), and the like.

[0023] The pharmaceutical composition of the present invention can be in a form formulated with the above active ingredient and a pharmaceutically acceptable carrier or additive commonly used in the pharmaceutical formulation technology field. Examples of the above carrier or additive include excipients, disintegrants, binders, fluidizing agents, lubricants, colorants, pH adjusters, surfactants, stabilizers, flavoring agents, fragrances, and the like. These additives are used in amounts commonly used in the pharmaceutical formulation technology field.

[0024] Examples of the excipient include starches such as corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch, and porous starch; sugars or sugar alcohols such as lactose hydrate, refined sugar, fructose, glucose, mannitol, sorbitol, erythritol, xylitol, trehalose, maltitol, powdered reduced maltose syrup, and lactitol; anhydrous calcium hydrogen phosphate, crystalline cellulose, powdered cellulose, precipitated calcium carbonate, calcium carbonate, and the like. Examples of the disintegrant include carmellose, carmellose calcium, sodium carboxymethyl starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, sodium carboxymethyl starch, croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose (L-HPC), hydroxypropyl starch, and the like. Preferably, croscarmellose sodium and L-HPC are used. Examples of the binder include hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, copovidone, polyvinyl alcohol, gum arabic powder, methylcellulose, low-substituted hydroxypropyl cellulose, hypromellose, sodium carboxymethylcellulose, dextrin, partially pregelatinized starch, pullulan, gum arabic, agar, gelatin, tragacanth, sodium alginate, etc. Preferably, hydroxypropyl cellulose and hydroxypropyl methylcellulose are used. Examples of the fluidizing agent include light anhydrous silicic acid, hydrous silicon dioxide, kaolin, talc, etc. Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, etc. Examples of the coloring agent include yellow ferric oxide, ferric oxide, Food Blue No. 1, Food Blue No. 2, Food Yellow No. 4, Food Yellow No. 5, Food Green No. 3, Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Red No. 104, Food Red No. 105, Food Red No. 106, lake pigment, riboflavin, sodium riboflavin phosphate, etc. Examples of the pH adjuster include citric acid, phosphoric acid, carbonic acid, tartaric acid, fumaric acid, acetic acid, amino acids and their salts, etc. Examples of the surfactant include sodium lauryl sulfate, polysorbate 80, polyoxyethylene (160) polyoxypropylene (30) glycol, etc. Examples of the stabilizer include tocopherol, tetrasodium edetate, nicotinamide, cyclodextrins, etc. Examples of the flavoring agent include ascorbic acid, citric acid, tartaric acid, malic acid, sucralose, stevia extract, etc. Examples of the fragrance include L-menthol, peppermint oil, lemon oil, vanillin, etc. The above-mentioned carrier or additive may be used alone or in an appropriate mixture of two or more.

[0025] The formulation of the pharmaceutical composition of the present invention may be carried out by using general methods described in publications such as Granulation Handbook (edited by the Japan Society for Powder Technology, Ohmsha), Prescription Design of Oral Preparations (edited by Mitsuru Hashida, Professor of the Graduate School of Pharmaceutical Sciences, Kyoto University, Yakugyo Jiho Co., Ltd.), Compression Molding Technology of Powders (edited by the Powder Engineering, Formulation and Particle Design Division, Nikkan Kogyo Shimbun, Ltd.), and Pharmaceutical Machinery Technology Handbook (2nd Edition, edited by the Editorial Committee for the 20th Anniversary Publication of the Pharmaceutical Machinery Technology Research Society, Pharmaceutical Machinery Technology Research Society), and there are no special restrictions.

[0026] For example, when formulating the pharmaceutical composition of the present invention into tablets, after mixing and granulating the above active ingredient with a conventional pharmaceutically acceptable carrier or additive, it can be tabletted using various tableting machines generally used in the formulation (for example, rotary tableting machines, etc.) to obtain tablets. Also, when formulating the pharmaceutical composition of the present invention into capsules, after mixing and granulating the above active ingredient with a conventional pharmaceutically acceptable carrier or additive, the granulated product can be filled into capsules to obtain capsules.

[0027] The pharmaceutical composition of the present invention can take various dosage forms, but a solid dosage form is preferred. Examples of solid dosage forms include tablets (including plain tablets, coated tablets, film-coated tablets, sugar-coated tablets, thin-layer sugar-coated tablets, orally disintegrating tablets, chewable tablets, etc.), capsules (including soft capsules, hard capsules, etc.), granules, powders, and pills, and preferably tablets.

[0028] The above solid dosage forms may be coated by a conventional method using a commonly formulated coating base. For example, tablets may be coated using a coating base to obtain film-coated tablets. Examples of coating bases include water-soluble bases such as hydroxypropylmethylcellulose (hypromellose), hydroxypropylcellulose, methylcellulose, povidone, copovidone, polyvinyl alcohol, polyvinyl alcohol copolymer, macrogol, etc.; water-insoluble bases such as ethylcellulose; enteric bases such as hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, methacrylic acid copolymer, acrylic acid copolymer, carboxyvinyl polymer, etc.; gastric-soluble bases such as polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer, polyvinyl acetal diethylaminoacetate, etc.; and gum arabic, pullulan, carnauba wax, shellac, macrogols, glycerin fatty acid esters, magnesium stearate, etc. In the present invention, the coating base may be one kind or two or more kinds. Furthermore, a coating additive may be used for the coating. Examples of the coating additive include a light-shielding agent, a fluidizing agent, a coloring agent, a plasticizer, etc. Examples of the plasticizer include copovidone, polyethylene glycol, triethyl citrate, castor oil, polysorbate, etc.

[0029] The present invention also provides a method for suppressing the appearance deterioration of a pharmaceutical composition containing (a) diphenhydramine or a salt thereof, (b) dextromethorphan or a salt thereof, and (c) guaifenesin, which is characterized by blending at least one selected from the group consisting of (d) a silicic acid compound and magnesium stearate. Each requirement (each component, its usage amount, its usage ratio, etc.) in this method is as described for the pharmaceutical composition of the present invention.

Examples

[0030] The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.

[0031] (Examples 1 - 8 and Comparative Examples 1 - 3) The main drug components and additive components shown in Table 1 were each weighed in a predetermined amount and physically mixed in a mortar to obtain a mixture.

Table 1 - 1

Table 1 - 2

[0032] (Test Example) The mixtures obtained above (Examples 1 - 8 and Comparative Examples 1 - 3) were put into glass bottles, sealed, and stored at 60°C for 3 weeks. The properties of the mixtures after storage were compared and evaluated with those immediately after the start of storage.

Table 2 - 1

Table 2 - 2

[0033] As shown in Table 2, it was confirmed that in the group containing a silicate compound or magnesium stearate, the state of the mixture was maintained even after storage at 60°C for 3 weeks (Examples 1 - 8). On the other hand, in the group without a silicate compound or magnesium stearate, dissolution of the mixture was observed, and it was difficult to maintain the state as a mixture (Comparative Examples 1 - 3). From the above, it became clear that silicate compounds including calcium silicate and magnesium stearate have the effect of suppressing the interaction of diphenhydramine or its salt, dextromethorphan or its salt, and guaifenesin.

[0034] (Production Examples 1 - 7) Each component was mixed according to the formulation and mixing ratio shown in Section A of Table 3 below and tabletted to obtain core tablets. The obtained core tablets were coated according to the formulation shown in Section B to obtain coating agents.

Table 3

Industrial Applicability

[0035] According to the present invention, it is possible to provide a pharmaceutical composition in which wetting and / or dissolution due to the interaction of (a) diphenhydramine or a salt thereof, (b) dextromethorphan or a salt thereof, and (c) guaifenesin is suppressed by at least one selected from the group consisting of (d) a silicic acid compound and magnesium stearate, and deterioration of the appearance quality is suppressed.

Claims

1. A pharmaceutical composition comprising a simultaneous combination of (a) diphenhydramine or a salt thereof, (b) dextromethorphan or a salt thereof, and (c) guaifenesin, characterized by containing at least one selected from the group consisting of (d) a silicic acid compound and magnesium stearate.

2. The pharmaceutical composition according to claim 1, wherein, with respect to 1 part by mass of (b) dextromethorphan or a salt thereof, at least one selected from the group consisting of a silicic acid compound and magnesium stearate is 0.2 part by mass or more.

3. The pharmaceutical composition according to claim 1 or 2, wherein, with respect to 1 part by mass of (a) diphenhydramine or a salt thereof, at least one selected from the group consisting of a silicic acid compound and magnesium stearate is 0.2 part by mass or more.

4. The pharmaceutical composition according to any one of claims 1 to 3, wherein, with respect to 1 part by mass of (c) guaifenesin, at least one selected from the group consisting of a silicic acid compound and magnesium stearate is 0.2 part by mass or more.

5. The pharmaceutical composition according to any one of claims 1 to 4, wherein the content of at least one selected from the group consisting of a silicic acid compound and magnesium stearate is 0.05 to 50% by mass based on the whole composition.

6. The pharmaceutical composition according to any one of claims 1 to 5, wherein (a) diphenhydramine or a salt thereof is diphenhydramine hydrochloride.

7. The pharmaceutical composition according to any one of claims 1 to 6, wherein (b) dextromethorphan or a salt thereof is dextromethorphan hydrobromide hydrate.

8. The pharmaceutical composition according to any one of claims 1 to 7, wherein (d) the silicic acid compound is at least one selected from the group consisting of calcium silicate, light anhydrous silicic acid, hydrous silicon dioxide, magnesium aluminometasilicate, and silica.

9. The pharmaceutical composition according to any one of claims 1 to 8, which is used for treating colds.

10. The pharmaceutical composition according to any one of claims 1 to 9, wherein the dosage form of the pharmaceutical composition is tablets, capsules, granules, powders or pills.

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