Solid composition

Abstract

To provide a solid composition which suppresses the decrease in the content of loratadine with time even if containing ibuprofen and loratadine.SOLUTION: There is provided a solid composition which comprises (a) ibuprofen and (b) loratadine and further (c) at least one selected from the group consisting of carbocisteine, ambroxol and its salt, bromhexine and its salt, tranexamic acid, glycyrrhizic acid and its salt, tipepidine and its salt and dextromethorphan and its salt.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a solid composition containing ibuprofen and loratadine.

Background Art

[0002] Ibuprofen is effective for rheumatoid arthritis, arthralgia and arthritis, neuralgia and neuritis, low back pain, cervical spondylosis, adnexitis, dysmenorrhea, erythema (erythema nodosum, polymorphic exudative erythema, erythema annulare centrifugum), and is also effective for antipyretic and analgesic effects of acute upper respiratory tract inflammation (including acute upper respiratory tract inflammation accompanied by acute bronchitis). In addition to antipyretic and analgesic drugs, it is widely formulated as an antipyretic and analgesic component of a general cold medicine (Non-Patent Document 1).

[0003] Loratadine is a second-generation histamine H1 receptor antagonist (second-generation antihistamine drug), which is effective for pruritus associated with allergic rhinitis, urticaria, and skin diseases (eczema / dermatitis, cutaneous pruritus), and has been approved as a switch OTC component (Non-Patent Document 2).

[0004] Carbocisteine has a mucus component regulating effect, goblet cell hyperplasia inhibitory effect, airway inflammation inhibitory effect, and mucosal normalization effect, and is widely known as a compound having excellent expectorant effects on upper respiratory tract inflammation (pharyngitis, laryngitis), acute bronchitis, bronchial asthma, chronic bronchitis, bronchiectasis, and pulmonary tuberculosis, and is widely formulated in general cold medicines and antitussive and expectorant drugs (Non-Patent Document 3).

[0005] Ambroxol and its salts have a promoting effect on the secretion of pulmonary surfactant, a promoting effect on the secretion of airway fluid, and a ciliary motility enhancing effect, and are widely known as compounds having excellent expectorant effects on acute bronchitis, bronchial asthma, chronic bronchitis, bronchiectasis, pulmonary tuberculosis, pneumoconiosis, and difficulty in expectoration after surgery. It has also been approved as a switch OTC component and is formulated in general cold medicines (Non-Patent Document 4).

[0006] Bromhexine and its salts are widely known as compounds having an expectorant effect excellent for acute bronchitis, chronic bronchitis, pulmonary tuberculosis, pneumoconiosis, and after surgery, by having an effect of increasing serous secretion, an effect of dissolving and reducing acidic glycoprotein, an effect of promoting the secretion of pulmonary surfactant, and an effect of enhancing ciliary movement, and are widely formulated in general cold remedies and antitussive expectorants (Non-Patent Document 5).

[0007] Tranexamic acid has anti-allergic and anti-inflammatory effects and shows excellent effects on symptoms such as sore throat, redness, congestion, and swelling in tonsillitis and pharyngolaryngitis, and is therefore widely formulated in general cold remedies, antitussive expectorants, nasal medications, etc. (Non-Patent Document 6).

[0008] Glycyrrhizic acid and its salts are widely known as components contained in licorice, and have anti-inflammatory, anti-allergic, and cell repair effects, and are known to have effects as digestive ulcers and expectorants. It is also widely formulated as a sweetening agent and flavoring agent (Non-Patent Document 7).

[0009] Tipepidine and its salts exhibit an antitussive effect by suppressing the cough center in the medulla oblongata and reducing the sensitivity to cough, and exhibit an expectorant effect by enhancing bronchial gland secretion and enhancing the movement of airway mucosal ciliated epithelium. It is widely used for cough and difficulty in expectoration associated with colds, upper respiratory tract infections (pharyngolaryngitis, rhinitis), acute bronchitis, chronic bronchitis, pneumonia, pulmonary tuberculosis, and bronchiectasis (Non-Patent Document 8).

[0010] Dextromethorphan and its salts are compounds that directly act on the cough center in the medulla oblongata and suppress the cough reflex, and are widely used for coughs associated with colds, acute bronchitis, chronic bronchitis, bronchiectasis, pneumonia, pulmonary tuberculosis, and upper respiratory tract infections (pharyngolaryngitis, rhinitis) (Non-Patent Document 9).

[0011] Hitherto, a capsule preparation in which ibuprofen, loratadine, and cyclodextrin are blended in a base containing polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, macrogol, and water has been known (Patent Document 1). In this document, a method of solving the decrease in solubility due to crystallization of loratadine by the coexistence of cyclodextrin is shown. However, this technique requires a step of dissolving or dispersing loratadine in a base containing a special solvent and water, the available formulations are limited to soft capsules, and its manufacturing process is also limited.

[0012] Hitherto, it has not been known whether an interaction that directly affects the decrease in the content of loratadine occurs between ibuprofen and loratadine.

Prior Art Documents

Non-Patent Documents

[0013]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Non-Patent Document 7

Non-Patent Document 8

Non-Patent Document 9

Patent Document

[0014]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0015] When the present inventors produced a solid composition containing ibuprofen and loratadine, they obtained a surprising finding that the content of loratadine decreased over time. The present invention has been made in view of the above circumstances, and an object thereof is to provide a solid composition in which, even when containing ibuprofen and loratadine, the decrease in the content of loratadine over time is suppressed.

Means for Solving the Problems

[0016] As a result of intensive studies by the present inventors, it was found that, unexpectedly, when at least one selected from the group consisting of carbocysteine, ambroxol and its salts, bromhexine and its salts, tranexamic acid, glycyrrhizic acid and its salts, tipepidine and its salts, and dextromethorphan and its salts is contained, the decrease in the content of loratadine over time can be suppressed, and the present invention has been completed.

[0017] That is, the present invention is (1)(a) Ibuprofen, (b) Loratadine, (c) Carbocisteine, Ambroxol and its salts, Bromhexine and its salts, Tranexamic acid, Glycyrrhizic acid and its salts, Tipepidine and its salts, and Dextromethorphan and its salts, a solid composition characterized by containing at least one selected from the group consisting of (2) The solid composition according to (1), wherein the salt of (c) Ambroxol is Ambroxol hydrochloride (3) The solid composition according to (1), wherein the salt of (c) Bromhexine is Bromhexine hydrochloride (4) The solid composition according to (1), wherein the salt of (c) Glycyrrhizic acid is Dipotassium glycyrrhizinate (5) The solid composition according to (1), wherein the salt of (c) Tipepidine is Tipepidine hibenzate (6) The solid composition according to (1), wherein the salt of (c) Dextromethorphan is Dextromethorphan hydrobromide hydrate (7) The solid composition according to any one of (1) to (6), wherein the dosage form is tablets, powders, fine granules, granules, pills, or capsules (8) Use of at least one selected from the group consisting of (c) Carbocisteine, Ambroxol and its salts, Bromhexine and its salts, Tranexamic acid, Glycyrrhizic acid and its salts, Tipepidine and its salts, and Dextromethorphan and its salts for producing a solid composition containing (a) Ibuprofen and (b) Loratadine, and in which (b) Loratadine is stabilized (9) Use of at least one selected from the group consisting of (c) Carbocisteine, Ambroxol and its salts, Bromhexine and its salts, Tranexamic acid, Glycyrrhizic acid and its salts, Tipepidine and its salts, and Dextromethorphan and its salts for stabilizing (b) Loratadine in a solid composition containing (a) Ibuprofen and (b) Loratadine is.

Advantages of the Invention

[0018] According to the present invention, it has become possible to provide a solid composition containing ibuprofen and loratadine and having excellent stability of loratadine.

Mode for Carrying Out the Invention

[0019] The ibuprofen used in the present invention is a compound represented by the chemical formula C 13 H 18 O2, and there is no particular limitation as long as it is pharmaceutically acceptable. Ibuprofen can be produced by a known method, and commercially available products can also be used. The content of ibuprofen in the solid composition of the present invention is not particularly limited as long as it exhibits the medicinal effect, but is usually 5 to 95% by mass, preferably 10 to 90% by mass, 15 to 85% by mass, 15 to 80% by mass, 20 to 70% by mass, 20 to 60% by mass.

[0020] The loratadine used in the present invention is a compound represented by the chemical formula C 22 H 23 ClN2O2, and there is no particular limitation as long as it is pharmaceutically acceptable. Loratadine can be produced by a known method, and commercially available products can also be used. The content of loratadine in the solid composition of the present invention is not particularly limited as long as it exhibits the medicinal effect, but is usually 0.001 to 50% by mass, 0.01 to 30% by mass, preferably 0.1 to 10% by mass, 0.2 to 7% by mass.

[0021] The carbocisteine used in the present invention is a compound represented by the chemical formula C5H9NO4S, and there is no particular limitation as long as it is pharmaceutically acceptable, but usually L-carbocisteine is used. Carbocisteine can be produced by a known method, and commercially available products can also be used. The content of carbocisteine in the solid composition of the present invention is not particularly limited, but is usually 1 to 95% by mass, 5 to 85% by mass, preferably 10 to 65% by mass.

[0022] The ambroxol used in the present invention is a compound represented by the chemical formula C 13 H 18A compound represented by Br2N2O or a salt thereof, and one of these may be used alone or two or more thereof may be used in combination. Such ambroxol or a salt thereof can be produced by a known method, and commercially available products can also be used. Further, ambroxol or a salt thereof is not particularly limited as long as it is pharmaceutically acceptable, but the salt includes, for example, salts of inorganic acids such as hydrochloride, hydrobromide, and phosphate, and organic acid salts such as acetate, oxalate, malonate, succinate, fumarate, maleate, lactate, malate, citrate, tartrate, and carbonate. Particularly preferred is hydrochloride. The content of ambroxol or a salt thereof in the solid composition of the present invention (when two or more of ambroxol or a salt thereof are contained, the total content thereof, the same shall apply hereinafter) is not particularly limited as long as it exhibits the medicinal effect, but is usually 0.01 to 50% by mass, preferably 0.1 to 30% by mass.

[0023] The bromhexine used in the present invention has the chemical formula C 14 H 20 A compound represented by Br2N2 or a salt thereof, and one of these may be used alone or two or more thereof may be used in combination. Such bromhexine or a salt thereof can be produced by a known method, and commercially available products can also be used. Further, bromhexine or a salt thereof is not particularly limited as long as it is pharmaceutically acceptable, but the salt includes, for example, salts of inorganic acids such as hydrochloride, hydrobromide, and phosphate, and organic acid salts such as acetate, oxalate, malonate, succinate, fumarate, maleate, lactate, malate, citrate, tartrate, and carbonate. Particularly preferred is hydrochloride. The content of bromhexine or a salt thereof in the solid composition of the present invention (when two or more of bromhexine or a salt thereof are contained, the total content thereof, the same shall apply hereinafter) is not particularly limited as long as it exhibits the medicinal effect, but is usually 0.01 to 30% by mass, preferably 0.1 to 30% by mass, 0.2 to 30% by mass.

[0024] The tranexamic acid used in the present invention has the chemical formula C8H 15It is a compound represented by NO2 and is not particularly limited as long as it is pharmaceutically acceptable. Tranexamic acid can be produced by known methods or commercially available products can be used. The content of tranexamic acid in the preparation of the present invention is not particularly limited as long as it exhibits its medicinal effect, but is usually 1 to 95% by mass, 3 to 95% by mass, preferably 5 to 70% by mass, 8 to 85% by mass, 10 to 65% by mass.

[0025] Glycyrrhizic acid or a salt thereof in the present invention is widely known as a component contained in licorice, can be obtained commercially, or can be produced by known production methods, and may be derived from crude drugs. Glycyrrhizic acid or a salt thereof may be the component itself or may be contained in crude drugs or traditional Chinese medicines. In particular, as a crude drug containing glycyrrhizic acids, licorice (licorice extract or licorice powder) can be used. In licorice, glycyrrhizic acid exists in both the free acid and salt forms. The salt of glycyrrhizic acid is not particularly limited as long as it is a pharmaceutically acceptable salt. Examples include trisodium glycyrrhizate, disodium glycyrrhizate, diammonium glycyrrhizate, monoammonium glycyrrhizate, dipotassium glycyrrhizate, and monopotassium glycyrrhizate. As glycyrrhizic acid and its salts, preferably glycyrrhizic acid and dipotassium glycyrrhizate, and particularly preferably dipotassium glycyrrhizate. The content of glycyrrhizic acid and its salts in the solid composition of the present invention (when two or more kinds of glycyrrhizic acid and its salts are included, the total amount thereof, the same applies hereinafter) is not particularly limited as long as it exhibits its medicinal effect, but is usually 0.01 to 50% by mass as glycyrrhizic acid, preferably 0.1 to 30% by mass.

[0026] Tipepidine used in the present invention has the chemical formula C 15 H 17A compound represented by NS2 or a salt thereof, and one of these may be used alone or two or more thereof may be used in combination. Such tipepidine or a salt thereof can be produced by a known method, and commercially available products can also be used. Further, tipepidine or a salt thereof is not particularly limited as long as it is pharmaceutically acceptable, but the salt includes, for example, salts of inorganic acids such as hydrochloride, hydrobromide, and phosphate, and acetates, oxalates, malonates, succinates, fumarates, maleates, lactates, malates, citrates, tartrates, hibenzates, carbonates, and other organic acid salts. Particularly preferred is hibenzate. The content of tipepidine or a salt thereof in the solid composition of the present invention (when two or more of tipepidine or a salt thereof are contained, the total content thereof, the same shall apply hereinafter) is not particularly limited as long as it is an amount showing its medicinal effect, but is usually 0.1 to 50% by mass, 0.1 to 30% by mass, preferably 1 to 30% by mass.

[0027] The dextromethorphan used in the present invention is a compound represented by the chemical formula C 18 H 25 NO or a salt thereof, and one of these may be used alone or two or more thereof may be used in combination. Such dextromethorphan or a salt thereof can be produced by a known method, and commercially available products can also be used. Further, dextromethorphan or a salt thereof is not particularly limited as long as it is pharmaceutically acceptable, but the salt includes, for example, salts of inorganic acids such as hydrochloride, hydrobromide, and phosphate, and acetates, oxalates, malonates, succinates, fumarates, maleates, lactates, malates, citrates, tartrates, hydrobromide, phenolphthalein salts, carbonates, and other organic acid salts. Particularly preferred is hydrobromide. The content of dextromethorphan or a salt thereof in the solid composition of the present invention (when two or more of dextromethorphan or a salt thereof are contained, the total content thereof, the same shall apply hereinafter) is not particularly limited as long as it is an amount showing its medicinal effect, but is usually 0.1 to 50% by mass, preferably 0.5 to 30% by mass.

[0028] In addition, the mixing ratio of (a) ibuprofen and (b) loratadine is not particularly limited, but it is preferably 10 parts by mass or more of ibuprofen with respect to 1 part by mass of loratadine. This is because the decrease in the content of loratadine over time becomes significant. The upper limit is not particularly limited, and it may be 60 parts by mass or 20 parts by mass.

[0029] In addition, from the viewpoint of the effects of the invention, the mixing ratio of (a) loratadine and (c) carbocisteine is preferably 4 parts by mass or more of carbocisteine with respect to 1 part by mass of loratadine, and may be 25 parts by mass or more. Also, the upper limit is not particularly limited and may be 75 parts by mass.

[0030] From the viewpoint of the effects of the invention, the mixing ratio of (a) loratadine and (c) ambroxol and its salts is preferably 1.5 parts by mass or more of ambroxol and its salts with respect to 1 part by mass of loratadine, and may be 4 parts by mass or more. Also, the upper limit is not particularly limited and may be 10 parts by mass or 4.5 parts by mass.

[0031] From the viewpoint of the effects of the invention, the mixing ratio of (a) loratadine and (c) bromhexine and its salts is preferably 0.2 parts by mass or more of bromhexine and its salts with respect to 1 part by mass of loratadine, more preferably 0.26 parts by mass or more, and may be 0.4 parts by mass or more. The upper limit is not particularly limited and may be 4 parts by mass or 1.2 parts by mass.

[0032] From the viewpoint of the effects of the invention, the mixing ratio of (a) loratadine and (c) tranexamic acid is preferably 4 parts by mass or more of tranexamic acid with respect to 1 part by mass of loratadine, and may be 9.3 parts by mass or more. The upper limit is not particularly limited and may be 100 parts by mass or 75 parts by mass.

[0033] From the viewpoint of the effects of the invention, the mixing ratio of (a) loratadine and (c) glycyrrhizic acid and its salts is preferably 0.1 parts by mass or more of glycyrrhizic acid with respect to 1 part by mass of loratadine, more preferably 1.2 parts by mass or more, and may be 2.4 parts by mass. The upper limit is not particularly limited and may be 10 parts by mass or 6 parts by mass.

[0034] (a) The mixing ratio of loratadine and (c) tipepidine and its salts is preferably 1 part by mass or more, more preferably 2.5 parts by mass or more, and may be 4 parts by mass or more of tipepidine and its salts with respect to 1 part by mass of loratadine from the viewpoint of the effects of the invention. The upper limit is not particularly limited, and it may be 10 parts by mass or 7.5 parts by mass.

[0035] (a) The mixing ratio of loratadine and (c) dextromethorphan and its salts is preferably 0.5 part by mass or more, more preferably 1.6 parts by mass or more of dextromethorphan and its salts with respect to 1 part by mass of loratadine from the viewpoint of the effects of the invention. The upper limit is not particularly limited, and it may be 10 parts by mass, 4 parts by mass, or 5 parts by mass.

[0036] In the solid composition of the present invention, other commonly used active ingredients, excipients, disintegrants, binders, fluidizing agents, lubricants, cooling agents, coloring agents, flavoring agents, flavoring agents, coating agents, etc. can be blended within a qualitative and quantitative range that does not impair the effects of the present invention.

[0037] Examples of other active ingredients that can be incorporated into the solid composition of the present invention include antipyretic analgesics, antihistamines, antitussives, noscapines, bronchodilators, expectorants, hypnotic sedatives, vitamins, anti-inflammatory agents, gastric mucosal protectants, crude drugs, traditional Chinese medicine prescriptions, caffeine, etc., and one or more selected from the group consisting of these may be contained.

[0038] Examples of excipients that can be incorporated into the solid composition of the present invention include lactose, starches, crystalline cellulose, sucrose, sugar alcohols, etc. Examples of disintegrants include low-substituted hydroxypropyl cellulose, sodium starch glycolate, crospovidone, carmellose, sodium carmellose, calcium carmellose, pregelatinized starch, etc. Examples of binders include hydroxypropyl cellulose, hypromellose, gelatin, pregelatinized starch, polyvinylpyrrolidone, pullulan, etc. Examples of fluidizing agents include light anhydrous silicic acid, hydrous silicon dioxide, etc. Examples of lubricants include sucrose fatty acid esters, hydrogenated oils, stearic acid, magnesium stearate, calcium stearate, etc. Examples of cooling agents include menthol, peppermint oil, eucalyptus oil, etc.

[0039] The solid composition of the present invention can be produced by a conventional method, and the method is not particularly limited. For example, (a) ibuprofen (hereinafter also referred to as component (a)), (b) loratadine (hereinafter also referred to as component (b)), (c) at least one selected from the group consisting of carbocisteine, ambroxol and its salts, bromhexine and its salts, tranexamic acid, glycyrrhizic acid and its salts, tipepidine and its salts, and dextromethorphan and its salts (hereinafter also referred to as component (c)) may simply be mixed, granulated after mixing, or the obtained granulated product may be coated. Further, components (a), (b) or (c) do not necessarily have to be contained in the same granulated product. For example, after producing a granulated product containing component (a) and component (c), component (b) is mixed, or after producing a granulated product containing component (a) and component (b), component (c) is mixed, or after producing a granulated product containing component (a) and component (c) and a granulated product containing component (b) and component (c), the two granulated products are mixed, etc.

[0040] The granulation method is not particularly limited, and it can be produced by a wet granulation method, a dry granulation method, a melt granulation method, etc., but preferably a wet granulation method. Examples of the wet granulation method include a stirring granulation method, a fluidized bed granulation method, a kneading granulation method, an extrusion granulation method, and a rolling fluidization granulation method. Further, conventional pharmaceutical additives such as the above active ingredient and excipient may be appropriately blended into the obtained granulated product. Further, the mixture thus obtained can be tabletted into tablets. When producing tablets, it may be produced by a direct tabletting method.

[0041] The solid composition of the present invention is not particularly limited as long as it is a dosage form defined in the general rules of pharmaceutical preparations of the Japanese Pharmacopoeia, but is preferably tablets, powders, fine granules, granules, pills, capsules (preferably hard capsules). Tablets defined in the general rules of pharmaceutical preparations of the Japanese Pharmacopoeia include orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets and soluble tablets, film-coated tablets, sugar-coated tablets, nucleated tablets, laminated tablets, etc. Further, a scored line, a mark for improving distinguishability, or an imprint can be provided on the tablet. Furthermore, the tablets of this preparation may be round tablets or shaped tablets.

Examples

[0042] Examples, control examples, and comparative examples are given below to explain the present invention in more detail, but the present invention is not limited to these examples and the like. (Control Example 1) An appropriate amount of a water / alcohol mixture was added to loratadine and mixed, and then dried to obtain a composition. (Comparative Example 1) 10 parts by mass of ibuprofen was weighed and mixed with 1 part by mass of loratadine, an appropriate amount of a water / alcohol mixture was added thereto and mixed, and then dried to obtain a composition. (Comparative Example 2) 4 parts by mass of lactose and 10 parts by mass of ibuprofen were weighed and mixed with 1 part by mass of loratadine, an appropriate amount of a water / alcohol mixture was added thereto and mixed, and then dried to obtain a composition. (Comparative Example 3) 1 part by mass of loratadine, 10 parts by mass of ibuprofen and 4 parts by mass of crystalline cellulose were weighed and mixed, an appropriate amount of a water / alcohol mixture was added thereto, and after mixing, the mixture was dried to obtain a composition. (Example 1) 1 part by mass of loratadine, 10 parts by mass of ibuprofen and 4 parts by mass of L-carbocysteine were weighed and mixed, an appropriate amount of a water / alcohol mixture was added thereto, and after mixing, the mixture was dried to obtain a composition. (Example 2) 1 part by mass of loratadine, 10 parts by mass of ibuprofen and 4 parts by mass of ambroxol hydrochloride were weighed and mixed, an appropriate amount of a water / alcohol mixture was added thereto, and after mixing, the mixture was dried to obtain a composition. (Example 3) 1 part by mass of loratadine, 10 parts by mass of ibuprofen and 4 parts by mass of bromhexine hydrochloride were weighed and mixed, an appropriate amount of a water / alcohol mixture was added thereto, and after mixing, the mixture was dried to obtain a composition. (Example 4) 1 part by mass of loratadine, 10 parts by mass of ibuprofen and 4 parts by mass of tranexamic acid were weighed and mixed, an appropriate amount of a water / alcohol mixture was added thereto, and after mixing, the mixture was dried to obtain a composition. (Example 5) 1 part by mass of loratadine, 10 parts by mass of ibuprofen and 4 parts by mass of dipotassium glycyrrhizinate (2.4 parts by mass as glycyrrhizic acid) were weighed and mixed, an appropriate amount of a water / alcohol mixture was added thereto, and after mixing, the mixture was dried to obtain a composition. (Example 6) 1 part by mass of loratadine, 10 parts by mass of ibuprofen and 4 parts by mass of tipepidine hibenzate were weighed and mixed, an appropriate amount of a water / alcohol mixture was added thereto, and after mixing, the mixture was dried to obtain a composition. (Example 7) 1 part by mass of loratadine, 10 parts by mass of ibuprofen and 4 parts by mass of dextromethorphan hydrobromide hydrate were weighed and mixed, an appropriate amount of a water / alcohol mixture was added thereto, and after mixing, the mixture was dried to obtain a composition.

[0043] (Test method) The compositions of the control example, comparative examples, and examples were stored at 65°C for 14 days, and the residual rate of loratadine in the compositions after 14 days was evaluated by HPLC method. Table 1 shows the residual rate (%) of loratadine after storage at 65°C for 14 days.

[0044]

Table 1

[0045] As shown in Table 1, a decrease in the content of loratadine was confirmed in Comparative Examples 1 to 3 in which ibuprofen and loratadine were blended. On the other hand, in Examples 1 to 7 in which L-carbocysteine, ambroxol hydrochloride, bromhexine hydrochloride, tranexamic acid, dipotassium glycyrrhizinate, tipepidine hibenzate, and dextromethorphan hydrobromide hydrate were blended, a decrease in the content of loratadine could be suppressed.

[0046] Examples, control examples, and comparative examples are given below to explain the present invention in more detail, but the present invention is not limited to these examples and the like. (Comparative Example 4) 20 parts by mass of ibuprofen was weighed and mixed with 1 part by mass of loratadine, and an appropriate amount of a water / alcohol mixture was added thereto, mixed, and then dried to obtain a composition. (Example 8) 20 parts by mass of ibuprofen and 25 parts by mass of L-carbocysteine were weighed and mixed with 1 part by mass of loratadine, and an appropriate amount of a water / alcohol mixture was added thereto, mixed, and then dried to obtain a composition. (Example 9) 20 parts by mass of ibuprofen and 1.5 parts by mass of ambroxol hydrochloride were weighed and mixed with 1 part by mass of loratadine, and an appropriate amount of a water / alcohol mixture was added thereto, mixed, and then dried to obtain a composition. (Example 10) 20 parts by mass of ibuprofen and 0.4 parts by mass of bromhexine hydrochloride were weighed and mixed with 1 part by mass of loratadine, and an appropriate amount of a water / alcohol mixture was added thereto, mixed, and then dried to obtain a composition. (Example 11) Weighed out and mixed 20 parts by mass of ibuprofen and 9.3 parts by mass of tranexamic acid with respect to 1 part by mass of loratadine, added an appropriate amount of a water / alcohol mixture thereto, mixed, and then dried to obtain a composition. (Example 12) Weighed out and mixed 20 parts by mass of ibuprofen and 2 parts by mass of dipotassium glycyrrhizinate (1.2 parts by mass as glycyrrhizic acid) with respect to 1 part by mass of loratadine, added an appropriate amount of a water / alcohol mixture thereto, mixed, and then dried to obtain a composition. (Example 13) Weighed out and mixed 20 parts by mass of ibuprofen and 2.5 parts by mass of tipepidine hibenzate with respect to 1 part by mass of loratadine, added an appropriate amount of a water / alcohol mixture thereto, mixed, and then dried to obtain a composition. (Example 14) Weighed out and mixed 20 parts by mass of ibuprofen and 1.6 parts by mass of dextromethorphan hydrobromide hydrate with respect to 1 part by mass of loratadine, added an appropriate amount of a water / alcohol mixture thereto, mixed, and then dried to obtain a composition.

[0047] (Test method) The compositions of the comparative examples and examples were stored at 65°C for 14 days, and the residual rate of loratadine in the composition after 14 days was evaluated by the HPLC method. Table 2 shows the residual rate of loratadine (%) after storage at 65°C for 14 days.

[0048]

Table 2

[0049] As shown in Table 2, a decrease in the content of loratadine was confirmed in Comparative Example 4 in which ibuprofen and loratadine were formulated. On the other hand, in Examples 8 to 14 in which L-carbocysteine, ambroxol hydrochloride, bromhexine hydrochloride, tranexamic acid, dipotassium glycyrrhizinate, tipepidine hibenzate, and dextromethorphan hydrobromide hydrate were formulated, a decrease in the content of loratadine could be suppressed.

[0050] Examples are given below to explain the present invention in more detail, but the present invention is not limited to these examples and the like. (Example 15) 20 parts by mass of ibuprofen and 0.2 parts by mass of bromhexine hydrochloride were weighed and mixed with 1 part by mass of loratadine, and an appropriate amount of a water / alcohol mixture was added thereto, followed by mixing and drying to obtain a composition. (Example 16) 20 parts by mass of ibuprofen and 1 part by mass of tipepidine hibenzate were weighed and mixed with 1 part by mass of loratadine, and an appropriate amount of a water / alcohol mixture was added thereto, followed by mixing and drying to obtain a composition. (Example 17) 20 parts by mass of ibuprofen and 0.5 part by mass of dextromethorphan hydrobromide hydrate were weighed and mixed with 1 part by mass of loratadine, and an appropriate amount of a water / alcohol mixture was added thereto, followed by mixing and drying to obtain a composition.

[0051] (Test method) The compositions of the examples were stored at 65°C for 14 days, and the residual rate of loratadine in the compositions after 14 days was evaluated by HPLC. Table 3 shows the residual rate (%) of loratadine after storage at 65°C for 14 days.

[0052]

Table 3

[0053] As shown in Table 3, the decrease in the content of loratadine (Comparative Example 4) confirmed when ibuprofen and loratadine were formulated could be suppressed in Examples 15 to 17 formulated with bromhexine hydrochloride, tipepidine hibenzate, and dextromethorphan hydrobromide hydrate.

[0054] Formulation preparation examples are given below. Formulation Examples 1 to 12 For the formulation examples described in Tables 4 and 5, tablets, powders or granules are produced using known techniques. The obtained powders or granules are filled into hard capsules using known techniques to produce hard capsule preparations.

[0055]

Table 4

[0056]

Table 5

Industrial Applicability

[0057] According to the present invention, it has become possible to provide a solid composition containing ibuprofen and loratadine and having excellent stability of loratadine.

Claims

**Claim 1** A solid composition comprising: (a) ibuprofen, (b) loratadine, and (c) ambroxol or a salt thereof. **Claim 2** The solid composition according to claim 1, wherein the salt of (c) ambroxol is ambroxol hydrochloride. **Claim 3** The solid composition according to claim 1 or 2, wherein the dosage form is a tablet, powder, fine granule, granule, pill, or capsule. **Claim 4** Use of (c) ambroxol or a salt thereof for producing a solid composition comprising (a) ibuprofen and (b) loratadine, wherein (b) loratadine is stabilized. **Claim 5** Use of (c) ambroxol or a salt thereof for stabilizing (b) loratadine in a solid composition comprising (a) ibuprofen and (b) loratadine.

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