JP2021075530A - Pharmaceutical composition - Google Patents

Abstract

To provide a pharmaceutical composition that suppresses wetting and/or dissolving due to the interaction of ibuprofen, dextromethorphan or a salt thereof and guaifenesin, which are concurrently blended, and suppresses degradation of appearance quality.SOLUTION: A pharmaceutical composition contains ibuprofen, dextromethorphan or a salt thereof, and guaifenesin, and tranexamic acid or a salt thereof.SELECTED DRAWING: None

Description

The present invention relates to pharmaceutical compositions containing ibuprofen.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) classified as a propionic acid system, and by inhibiting cyclooxygenase (COX), it suppresses the production of prostaglandins and exhibits an antipyretic analgesic effect. Ibuprofen is widely distributed not only as a medical drug but also as an active ingredient of over-the-counter drugs such as common cold treatments.

In addition to ibuprofen, dextromethorphan, an antitussive, and guaifenesin, a sputum-removing agent, are known as agents used as active ingredients of common cold treatments.
Patent Document 1 discloses a water-suspendable pharmaceutical composition containing a granular composition useful as a pharmaceutical carrier that can be used for preparing a pharmaceutical composition capable of rapidly suspending in an aqueous medium. , Examples of pharmaceutically effective substances contained therein include ibuprofen, dextromethorphan, guaifenesin and the like.

Patent Document 2 discloses a method for producing a microemulsion concentrate for oral administration of a poorly soluble cold drug, and examples of the poorly soluble cold drug include ibuprofen, dextromethorphan, guaifenesin and the like.

Further, Patent Document 3 aims to enhance the action of caffeine and improve the usefulness of a common cold drug from the viewpoint of QOL while effectively utilizing the hypnotic action of antihistamines such as diphenhydramine. As a preparation, a combination preparation containing a first common cold drug prescribing an antihistamine and a second common cold drug prescribing another antihistamine having a different rate of occurrence of hypnotic action is disclosed. Further, as a preparation for the same purpose, Patent Document 4 describes a first common cold treatment drug in which an antihistamine is prescribed at a first dose, and a second dose of the antihistamine, which is different from the first dose. A combination formulation containing 2 common cold treatments is disclosed. These documents describe that the preparation may further contain ibuprofen, dextromethorphan, guaifenesin and the like.

JP 2000-508342 JP 2006-508104 JP-A-2007-302578 Japanese Patent Application Laid-Open No. 2008-100924

All of the above documents indicate that a plurality of active ingredients can be blended in a drug such as a common cold drug, but (a) ibuprofen, (b) dextromethorphan or a salt thereof, and (c) guaifenesin are used. When co-blended, the interaction of these agents causes wetting and / or dissolution, and there is no description or suggestion of a problem that impairs appearance quality.
An object of the present invention is to provide a pharmaceutical composition which suppresses wetting and / or dissolution due to interaction when the above three components (a) to (c) are simultaneously blended and suppresses deterioration of appearance quality. ..

As a result of diligent studies, the present inventor has found that the above problems can be solved by blending tranexamic acid or a salt thereof in addition to the above three components (a) to (c), and has completed the present invention. ..
That is, the present invention includes the following aspects.
[1] A pharmaceutical composition comprising ibuprofen, dextromethorphan or a salt thereof, and guaifenesin, and tranexamic acid or a salt thereof.
[2] The pharmaceutical composition according to [1], wherein dextromethorphan or a salt thereof is dextromethorphan hydrobromide hydrate.
[3] The pharmaceutical composition according to [1] or [2], wherein tranexamic acid or a salt thereof is tranexamic acid.
[4] The pharmaceutical composition according to any one of [1] to [3], which is used for the common cold.
[5] The pharmaceutical composition according to any one of [1] to [4], wherein the dosage form of the pharmaceutical composition is a tablet, a capsule, a granule, a powder or a pill.

According to the present invention, in a pharmaceutical composition containing (a) ibuprofen, (b) dextromethorphan or a salt thereof, and (c) guaifenesin at the same time, tranexamic acid or a salt thereof may be further added to these agents. Wetting and / or dissolution due to the interaction of the above can be suppressed, and deterioration of appearance quality can be suppressed. Therefore, according to the present invention, it is possible to provide a pharmaceutical composition containing the above three components (a) to (c) and suppressing deterioration of appearance quality.

The pharmaceutical composition of the present invention is characterized by containing ibuprofen, dextromethorphan or a salt thereof, and guaifenesin, and tranexamic acid or a salt thereof.

The "ibuprofen" in the present invention can be produced by a known method, or a commercially available product can be used. For example, ibuprofen conforming to the Japanese Pharmacopoeia can be used.
The dose of ibuprofen in the present invention may be appropriately examined and determined according to the age, symptoms, etc. of the user, and for example, 50 to 600 mg per day may be divided into 1 dose or 2 to 3 doses. It is preferable to administer.
The content of ibuprofen contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately examined and determined based on the above dose. For example, 1 to 60% by mass, preferably 1 to 60% by mass of the entire pharmaceutical composition. Is 5 to 50% by mass, more preferably 10 to 30% by mass.

The "dextromethorphan or a salt thereof" in the present invention refers to dextromethorphan and a pharmaceutically acceptable salt thereof, and a solvate of dextromethorphan and a pharmaceutically acceptable salt thereof and water, alcohol, etc. Including. Examples of dextromethorphan or a salt thereof include dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthaline salt and the like, and dextromethorphan hydrobromide hydrate is preferable. It is a thing. These can be produced by a known method, or commercially available products can be used. For example, dextromethorphan or a salt thereof according to the Japanese Pharmacopoeia can be used.
The dose of dextromethorphan or a salt thereof in the present invention may be appropriately examined and determined according to the age, symptoms, etc. of the user, and is, for example, 0.1 to 270 mg per day, preferably 0. It is preferable to administer 5 to 180 mg, more preferably 1 to 90 mg in a single dose or in 2 to 3 divided doses. When dextromethorphan or a salt thereof is dextromethorphan hydrobromide hydrate, the amount of dextromethorphan hydrobromide hydrate is 6 to 60 mg, preferably 15 to 60 mg per day. It is preferable to administer 20 to 60 mg. Further, when dextromethorphan or a salt thereof is dextromethorphanphenol phthalin salt, 9 to 90 mg, preferably 22 to 90 mg, more preferably 30 to 90 mg of dextromethorphan phenolphthalin salt is administered per day. It is preferable to do so.
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 examined and determined based on the above dose. For example, the entire pharmaceutical composition may be determined. It is 0.1 to 5% by mass, preferably 0.5 to 3% by mass.

The "guaifenesin" in the present invention can be produced by a known method, or a commercially available product can be used. For example, guaifenesin conforming to the Japanese Pharmacopoeia can be used.
The dose of guaifenesin in the present invention may be appropriately examined and determined according to the age, symptoms, etc. of the user, and for example, 20 to 600 mg per day may be divided into 1 dose or 2 to 3 doses. It is preferable to administer.
The content of guaifenesin contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately examined and determined based on the above dose. For example, 1 to 60% by mass, preferably 1 to 60% by mass of the entire pharmaceutical composition. Is 2.5 to 50% by mass, more preferably 5 to 30% by mass.

The "tranexamic acid or a salt thereof" in the present invention includes tranexamic acid and a pharmaceutically acceptable salt thereof, and a solvate of tranexamic acid and a pharmaceutically acceptable salt thereof and water, alcohol and the like. .. Examples of tranexamic acid or a salt thereof include tranexamic acid, mineral salts such as tranexamic acid hydrochloride, nitrate and sulfate, organic acid salts such as methanesulfonate, sodium salt, potassium salt, calcium salt and magnesium. Examples thereof include alkali metal salts such as salts and alkaline earth metal salts, and tranexamic acid is preferable. These can be produced by a known method, or commercially available products can be used. For example, tranexamic acid or a salt thereof according to the Japanese Pharmacopoeia can be used.
The dose of tranexamic acid or a salt thereof in the present invention may be appropriately examined and determined according to the age, symptoms, etc. of the user. For example, in the case of tranexamic acid, 50 to 2000 mg per day is 1 It is preferable to administer in divided doses or in 2 to 3 divided doses.
The content of tranexamic acid or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately examined and determined based on the above dose. For example, 1 to 80 of the entire pharmaceutical composition. It is by mass, preferably 5 to 60% by mass, and more preferably 10 to 40% by mass.

The mass ratio of ibuprofen to dextromethorphan or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, but for example, dextromethorphan or a salt thereof is the lower limit thereof with respect to 1 part by mass of ibuprofen. It is 0.01 parts by mass or more, preferably 0.02 parts by mass or more, and the upper limit thereof is 2 parts by mass or less, preferably 1.5 parts by mass or less.

The mass ratio of ibuprofen to guaifenecin contained in the pharmaceutical composition of the present invention is not particularly limited, but for example, guaifenecin is preferably 0.1 part by mass or more as the lower limit thereof with respect to 1 part by mass of ibuprofen. It is 0.5 parts by mass or more, and the upper limit thereof is 10 parts by mass or less, preferably 5 parts by mass or less.

The mass ratio of ibuprofen to tranexamic acid or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, but for example, tranexamic acid or a salt thereof is 0 as the lower limit thereof with respect to 1 part by mass of ibuprofen. .1 part by mass or more, preferably 0.5 part by mass or more, and the upper limit thereof is 10 parts by mass or less, preferably 5 parts by mass or less.

The mass ratio of dextrometholphan or a salt thereof and tranexamic acid or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, but for example, tranexamic acid or tranexamic acid or a salt thereof is based on 1 part by mass of dextrometholphan or a salt thereof. The lower limit of the salt is, for example, 1 part by mass or more, preferably 5 parts by mass or more, and the upper limit thereof is 100 parts by mass or less, preferably 20 parts by mass or less.

The mass ratio of guayphenesin to tranexamic acid or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, but for example, tranexamic acid or a salt thereof is 0 as the lower limit thereof with respect to 1 part by mass of guayphenesin. .1 part by mass or more, preferably 0.5 part by mass or more, and the upper limit thereof is 10 parts by mass or less, preferably 5 parts by mass or less.

The mass ratio of the combination of ibuprofen, dextrometholphan or a salt thereof and guayphenesin contained in the pharmaceutical composition of the present invention and tranexamic acid or a salt thereof is not particularly limited. The lower limit of the acid or its salt is, for example, 0.05 parts by mass or more, preferably 0.1 parts by mass, and the upper limit thereof is 10 parts by mass or less, preferably 5 parts by mass or less.

Wetting and / or dissolution when (a) ibuprofen, (b) dextromethorphan or a salt thereof, and (c) guaifenesin are co-blended, which are the subjects of the present invention, and the deterioration of the appearance quality based on the mixture are the components (a). It is considered that ~ (c) is caused by physical contact. Therefore, examples of the pharmaceutical composition of the present invention include pharmaceutical compositions in which the components (a) to (c) are not physically separated and are contained in a state where they can come into contact with each other. As such a pharmaceutical composition, for example, tablets obtained by mixing and granulating these components in the same group and tableting, or granulating these components in another group and then granulating them. Includes tablets and the like obtained by mixing powders and tableting.

The pharmaceutical composition of the present invention contains active ingredients other than the above active ingredients, for example, antihypertensive analgesics, rhinitis drugs, antihistamines, antitussives, sputum agents, bronchial dilators, gastric mucosa protection, as long as the effects of the present invention are not inhibited. Agents, vitamins, hypnotic sedatives, sputum-dissolving agents, anti-inflammatory agents, anticholinergic agents, crude drugs, Chinese herbal prescriptions, etc. may be blended.

Examples of the antipyretic analgesic include aspirin (acetylsalicylic acid), aspirin aluminum, acetaminophen, salicylamide, sodium salicylate, ethenzamide, sazapyrine, lactylphenetidine, ketoprofen, isopropylantipyrine, sodium loxoprofen and the like.
Examples of the drug for rhinitis include pseudoephedrine hydrochloride, chlorpheniramine dl-chlorpheniramine, d-chlorpheniramine maleate, belladonna total alkaloid, isopropamide iodide, dipotassium glycyrrhizinate and the like.
Antihistamines include, for example, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, alimemazine tartrate, isotipendyl hydrochloride, promethazine methylene disalicylate, diphenylpyraline hydrochloride, diphenylpyraline theocrate, isotipendyl hydrochloride, diferrol hydrochloride, phosphoric acid. Dipheterol, triprolysine hydrochloride hydrate, tryperenamine hydrochloride, tonsylamine hydrochloride, phenetazine hydrochloride, metodylazine hydrochloride, carbinoxamine diphenyldisulfonate, mebuhydrolin napadisylate, carbinoxamine maleate, iproheptin hydrochloride, promethazine hydrochloride, carbinoxamine diphenyldisulfonate Examples thereof include phenetazine, promethazine methylene disalicylate, cremastine fumarate, and mekitadine.
Examples of narcotic antitussives include codeine phosphate hydrate and dihydrocodeine phosphate.
Non-pharmaceutical antitussives include, for example, allocramid, isoamynyl, epradinone, oxerazine, clofedanol, clobutinol, cloperastin, dibunato, dimemorphan, tipepidin, noscapine, hydrocotarnin, pentoxyberin, beneproperin and hominoben, and salts and water thereof. Examples thereof include Japanese products, and examples of the salts and hydrates thereof include alloclamid hydrochloride, cloperastine hydrochloride, cloperastinfendizoate, dibunato sodium, dimemorphan phosphate, tipepidin hibenzate, and the like. Examples thereof include tipepidin citrate, pentoxyberin silicate and their hydrates.
Examples of the expectorant include potassium guayacol sulfonate, bromhexine hydrochloride, tipepidin citrate, L-carbocisteine, ammonium chloride, l-menthol, ammonia / uikyosei, potassium cresol sulfonate, and the like.
Bronchial dilators include, for example, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, trimetokinol hydrochloride, phenylpropanolamine hydrochloride, methoxyphenamine hydrochloride, l-methylephedrine hydrochloride, pseudoephedrine hydrochloride, aminophylline, diprophylline, Examples include theophylline and proxiphylline.
Examples of the gastromucosal protective agent include glycine, aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum / aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, and water. Aluminum oxide / magnesium carbonate mixed dry gel, co-precipitated product of aluminum hydroxide / sodium hydrogen carbonate, co-precipitated product of aluminum hydroxide / calcium carbonate / magnesium carbonate, co-precipitated product of magnesium hydroxide / potassium aluminum sulfate, Examples include magnesium carbonate.
Examples of vitamins include vitamin B ₁ or a derivative thereof or a salt thereof, vitamin B ₂ or a derivative thereof or a salt thereof, vitamin C or a derivative thereof or a salt thereof, vitamin P (hesperidin) or a derivative thereof. Alternatively, those salts and the like can be exemplified.
Examples of hypnotic sedatives include allylisopropylacetylurea and bromvalerylurea.
Examples of the sputum solubilizer include lysozyme chloride, L-ethylcysteine hydrochloride, and methylcysteine hydrochloride.
Examples of the anti-inflammatory agent include lysozyme chloride, seraptase, glycyrrhizic acid and salts thereof.
Examples of the anticholinergic agent include belladonna total alkaloids and isopropamide iodide.
Herbal medicines include Maou, Nantenjitsu, Ohi, Onji, Kanzo, Kikyo, Shazenshi, Shazensou, Sexan, Senega, Baimo, Fennel, Oubaku, Coptis chinensis, Zedoary, Kamitsure, Keihi, Gentiana, Goou, Beast (including Yutan). Examples thereof include shajin, fennel, licorice, clove, chimpi, zedoary, jiryu, chikusetsu carrot, and carrot.
Examples of Chinese medicine prescriptions include Neto, Neyu Kakikyo, Keikinto, Kososan, Saiko Keikinto, Shosaikoto, Shoseiryuto, Bakumondoto, Hangekobokuto, and Maoto.

The pharmaceutical composition of the present invention preferably does not contain caffeine.
Examples of caffeine include caffeine, caffeine hydrate, anhydrous caffeine, and pharmaceutically acceptable salts of caffeine (sodium benzoate caffeine, etc.).

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

Excipients include, for example, starches such as corn starch, potato starch, wheat costarch, rice starch, partially pregelatinized starch, pregelatinized starch, perforated starch; lactose hydrate, refined sucrose, fructose, glucose, mannitol. , Sorbitol, erythritol, xylitol, trehalose, martitol, powdered reduced starch sugar, sugars or sugar alcohols such as 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, carboxymethyl starch sodium, carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl starch sodium, croscarmellose sodium, crospovidone, and low degree of substitution hydroxypropyl cellulose (L-HPC). Hydroxypropyl starch or the like is used, preferably croscarmellose sodium, L-HPC.
Examples of the binder include hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, copolyvidone, polyvinyl alcohol, gum arabic powder, methyl cellulose, low-substituted hydroxypropyl cellulose, hypromellose, sodium carmellose, dextrin, partially pregelatinized starch, and purulan. , Arabic gum, canten, gelatin, tragant, sodium alginate and the like are used, and hydroxypropyl cellulose and hydroxypropyl methyl cellulose are preferable.
Examples of the fluidizing agent include light anhydrous silicic acid, hydrous silicon dioxide, calcium silicate, magnesium aluminometasilicate, kaolin, talc and the like.
Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, talc, and sucrose fatty acid ester.
Examples of colorants include yellow sesquioxide, iron sesquioxide, edible blue No. 1, edible blue No. 2, edible yellow No. 4, edible yellow No. 5, edible green No. 3, edible red No. 2, and edible red No. 3. , Edible red No. 102, edible red No. 104, edible red No. 105, edible red No. 106, edible lake pigment, riboflavin, sodium riboflavin phosphate, titanium oxide and the like.
Examples of the pH adjuster include citric acid, phosphoric acid, carbonic acid, tartaric acid, fumaric acid, acetic acid, amino acids and salts thereof.
Examples of the surfactant include sodium lauryl sulfate, polysorbate 80, polyoxyethylene (160) polyoxypropylene (30) glycol and the like.
Examples of the stabilizer include tocopherol, tetrasodium edetate, nicotinamide, cyclodextrins and the like.
Examples of the flavoring agent include ascorbic acid, citric acid, tartaric acid, malic acid, sucralose, stevia extract and the like.
Examples of the fragrance include L-menthol, peppermint oil, lemon oil, vanillin and the like.
The above-mentioned carrier or additive may be used alone or in combination of two or more as appropriate.

The formulation of the pharmaceutical composition of the present invention is described in the Granulation Handbook (edited by Japan Powder Industry Technology Association, Ohm Co., Ltd.), Prescription design of oral administration preparations (edited by Mitsuru Hashida, Professor, Graduate School of Pharmaceutical Sciences, Kyoto University, Pharmaceutical Industry Time Report) , Powder compression molding technology (powder engineering / formulation and particle design subcommittee edition, Nikkan Kogyo Shimbun), formulation machine technology handbook (2nd edition, formulation machine technology study group 20th anniversary publication editorial committee edition, formulation The general method described in publications such as the Mechanical Technology Study Group) may be used, and there are no special restrictions.

For example, when the pharmaceutical composition of the present invention is formulated into a tablet, after mixing and granulating the above active ingredient with a conventional pharmaceutically acceptable carrier or additive, various tableting machines generally used for the formulation (for example, , Rotary tableting machine, etc.) can be used to tablet and form tablets. When the pharmaceutical composition of the present invention is formulated into a capsule, the active ingredient and a conventional pharmaceutically acceptable carrier or additive are mixed and granulated, and then the granulated product is filled in a capsule to form a capsule. It can be used as an agent.

The pharmaceutical composition of the present invention may take various pharmaceutical forms, but a solid pharmaceutical composition is preferable. Examples of the solid preparation include tablets (including uncoated tablets, coated tablets, film-coated tablets, sugar-coated tablets, thin-layer sugar-coated tablets, orally disintegrating tablets, chewable tablets, etc.) and capsules (soft capsules, hard capsules, etc.). ), Granules, powders, pills, and preferably tablets.

The solid preparation may be coated by a conventional method with a coating base which is usually blended. For example, the tablet may be coated with a coating base to form a film-coated tablet.
Examples of the coating base include a water-soluble base such as hydroxypropylmethyl cellulose (hypromellose), hydroxypropyl cellulose, methyl cellulose, povidone, copolyvidone, polyvinyl alcohol, polyvinyl alcohol copolymer, macrogol, and a water-insoluble base such as ethyl cellulose. , Hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, hydroxypropylmethylcellulose acetate succinate, methacrylic acid copolymer, acrylic acid copolymer, enteric base such as carboxyvinyl polymer, polyvinyl acetal diethylamino Examples thereof include gastrosoluble bases such as acetate, aminoalkyl methacrylate copolymer, polyvinyl acetate diethylaminoacetate, gum arabic, purulan, carnauba wax, cellac, macrogol, glycerin fatty acid ester, magnesium stearate and the like.
Further, in the present invention, the coating base may be one kind or two or more kinds.
In addition, coating additives may be used for coating. Examples of the coating additive include a light-shielding agent, a fluidizing agent, a coloring agent, a plasticizer, and the like.
Examples of the plasticizer include copolyvidone, polyethylene glycol, triethyl citrate, castor oil, polysorbate and the like.

The present invention is a method for suppressing deterioration of the appearance of a pharmaceutical composition containing (a) ibuprofen, (b) dextromethorphan or a salt thereof, and (c) guaifenesin, and contains tranexamic acid or a salt thereof. It also provides a method characterized by this. Each requirement (each component, the amount used thereof, the ratio used thereof, etc.) in this method is as described for the pharmaceutical composition of the present invention.

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

(Examples 1 and 2 and Comparative Examples 1 and 2)
A predetermined amount of the main ingredient shown in Table 1 was weighed, granulated in a mortar using a small amount of purified water, and then dried to obtain a granulated product.

(Test example)
The granulated products obtained above (Examples 1 and 2 and Comparative Examples 1 and 2) were placed in a glass bottle, sealed tightly, and stored under 60 ° C. conditions for 1 week. The properties of the granulated product after storage were compared and evaluated with those immediately after the start of storage.

As shown in Table 2, it was confirmed that in the tranexamic acid-containing group, the state of the granulated product was maintained even when stored at 60 ° C. for 1 week (Examples 1 and 2). On the other hand, in the tranexamic acid-free group, wetting and melting of the granulated product were observed, and it was difficult to maintain the state of the granulated product (Comparative Examples 1 and 2).
From the above, it was clarified that tranexamic acid or a salt thereof has an effect of suppressing the interaction between ibuprofen, dextromethorphan or a salt thereof, and guaifenesin.

(Manufacturing Examples 1 to 5)
Each component was mixed according to the formulation and compounding ratio shown in Category A of Table 3 below, and tableted to obtain an uncoated tablet. The obtained uncoated tablets were coated according to the formulation shown in Category B to obtain a coating agent.

According to the present invention, tranexamic acid or a salt thereof suppresses wetting and / or dissolution due to the interaction of (a) ibuprofen, (b) dextromethorphan or a salt thereof, and (c) guaifenesin, resulting in deterioration of appearance quality. It is possible to provide a pharmaceutical composition in which is suppressed.

Claims (5)

A pharmaceutical composition comprising ibuprofen, dextromethorphan or a salt thereof, and guaifenesin, and tranexamic acid or a salt thereof. The pharmaceutical composition according to claim 1, wherein the dextromethorphan or a salt thereof is dextromethorphan hydrobromide hydrate. The pharmaceutical composition according to claim 1 or 2, wherein the tranexamic acid or a salt thereof is tranexamic acid. The pharmaceutical composition according to any one of claims 1 to 3, which is used for a cold. The pharmaceutical composition according to any one of claims 1 to 4, wherein the dosage form of the pharmaceutical composition is a tablet, a capsule, a granule, a powder or a pill.