JPH04327526A - Solid pharmaceutical for oral use - Google Patents

Abstract

PURPOSE:To obtain a solid pharmaceutical for oral use, capable of masking unpleasant taste and eliminating aftertaste having unpleasantness and useful in the field of foods, etc., by blending a substance having unpleasant taste with a foaming agent foaming in dissolution in the oral cavity. CONSTITUTION:A solid pharmaceutical for oral use is obtained by blending a substance such as a bitter ingredient such as caffeine, dimenhydrinate, chlorpheniramine maleate, diphenhydramine salicylate, diprophylline or pyridoxine hydrochloride having unpleasant taste with a foaming agent capable of foaming in dissolution in the oral cavity, preferably a combination of an ingredient capable of generating gaseous carbon dioxide by decomposition with its decomposing agent, e.g. a combination of a carbonate (e.g. sodium hydrogencarbonate) with an organic acid (e.g. malic acid, citric acid, tartaric acid, ascorbic acid or succinic acid). In the solid pharmaceutical, 1-10wt.% sodium hydrogencarbonate and 3-20wt.% organic acid are preferably blended. The resultant pharmaceutical is suitable for improving feeling of administering a medicine for internal use and palatability of a composition containing ingredients having unpleasant taste.

Description

Description: [0001] The present invention relates to improving the taste of oral solid preparations such as tablets, powders, and granules in the fields of pharmaceuticals and foods. [Prior Art] In bitter-tasting drugs such as pharmaceuticals,
Various methods are known for masking bitterness. Typical methods include a method of coating bitter components with sugar coating, a method of coating with a polymer substance that is poorly soluble or insoluble in water (Japanese Patent Laid-Open Nos. 58-4714, 1983-
129224) is known. However, with this method, the elution of the active ingredient from the drug may be delayed, resulting in a delay in its effect on the living body. In addition, a method of coating with a water-soluble polymer (Japanese Patent Application Laid-Open No. 126122/1982) is known, but this may also cause a delay in the elution of the drug, and after the coating material has dissolved, the medicinal properties remain It has the disadvantage of being bitter and leaving an unpleasant aftertaste. Furthermore, there is a method of simply adding a bitterness masking agent and a sweetener to the bitterness component (Japanese Patent Laid-Open No. 61-14
8129, JP-A-2-56416) are also known. However, although this method can alleviate the discomfort to some extent, it does not sufficiently improve the masking effect of the sweetener. Problems to be Solved by the Invention The present invention provides a method for dissolving ingredients that have an unpleasant taste such as bitterness without impairing their original solubility.
To provide a solid preparation for oral use that has excellent feeling of administration and no unpleasant aftertaste. [Means for Solving the Problems] As a result of intensive research aimed at improving the effect of masking unpleasant tastes such as bitterness and eliminating unpleasant aftertastes, the present inventors have developed a solid preparation. It has been found that the above object can be achieved by simultaneously dissolving and foaming in the oral cavity. That is, the oral solid preparation of the present invention is characterized in that a foaming agent that foams when dissolved in the oral cavity is added to the substance having an unpleasant taste. Embodiments of the Invention The foaming agent that foams when dissolved in the oral cavity used in the present invention is preferably a combination of a component that decomposes to generate carbon dioxide gas and this decomposition agent. Examples include a combination of a salt and a reducing agent such as an organic acid. [0008] A typical carbonate is sodium hydrogen carbonate. In addition, examples of organic acids include malic acid,
Citric acid, tartaric acid, ascorbic acid, succinic acid, etc.
It is used as a species or a mixture of two or more species. In the reaction between a carbonate and an organic acid, the hydrogen atoms of the organic acid reduce the carbonate, and as a result, the organic acid becomes a salt such as a sodium salt, and the carbonate releases water and carbon dioxide. This reaction is accelerated when the formulation dissolves in the oral cavity, but the carbon dioxide released is effervescent, effectively masking the unpleasant taste. [0010] Substances having a bitter taste that are the object of the present invention include anhydrous caffeine, caffeine, diprophylline,
Representative examples include diphenhydramine salicylate, chlorpheniramine maleate, pyridoxine hydrochloride, dimenhydrinate, meclizine hydrochloride, methylephedrine hydrochloride, potassium guaiacolsulfonate, guaifenesin, and chlorhexidine hydrochloride. [0011] Other substances with bitter taste that are the object of the present invention include dihydrocodeine phosphate, ephedrine hydrochloride, spironolactone, tegafur, erythromycin stearate, aracepril, sodium palproate, meclofenoxate hydrochloride, and chloramphenicol. ,
Aminophylline, erythromycin, calcium hopatenate, calcium pantothenate, phenobarbital,
Cimetidine, etilefrine hydrochloride, pirenzepine hydrochloride, butylscopolamine hydrochloride, diltiazem hydrochloride, enoxacin, pyromidic acid trihydrate, propranolol hydrochloride, flufenamic acid, chlorpromazine, digitoxin, promethazine hydrochloride, metoclopramide hydrochloride, ofloxacin,
These include sulpirin, acetaminophen, aspirin, and ibuprofen. Further, examples of substances having astringent taste include pendydamine hydrochloride, alprenolol hydrochloride, biphemeran hydrochloride, lidocaine, diphenhydramine hydrochloride, tolmetin sodium, nortriptyline hydrochloride, and loperamide hydrochloride. These substances generally have a bitter taste. [0013] In order to correct the taste of the preparation, sweeteners may be incorporated, such as sucrose, xylitol, mannitol, saccharin, sorbitol, and the like. [0014] In the present invention, the amount of sodium hydrogen carbonate used as a blowing agent is 0.5 to 20% by weight in the solid preparation.
Preferably 1 to 10% by weight, organic acid 1 to 40% by weight,
Preferably it is used in an amount of 3 to 20% by weight. Type 1 or 2
The amount of ingredients that have more unpleasant taste than seeds is usually 1 to 30%.
Weight%. [0015] The amount of the sweetener to be blended is determined depending on the intensity of sweetness, or, if a plurality of sweeteners are used, the blending ratio of the sweeteners. The amount of sucrose, xylitol, and mannitol is usually 10 to 75% by weight, preferably 50 to 75% by weight. When blending ingredients with very strong sweetness such as saccharin, it is used at 0.05 to 5% by weight, preferably 0.1 to 1% by weight, but when xylitol and mannitol are blended at this time, 20% by weight is used. ~50% by weight is preferred. [0016] In addition, the solid preparation of the present invention contains excipients commonly used in formulations (eg, lactose, starch, crystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyethylene glycol,
Magnesium stearate, etc.), flavoring agents (for example, menthol, etc.), fragrances, etc. may be appropriately blended. foaming agent,
The blending amount of substances having unpleasant taste, sweeteners, etc. is determined by the blending ratio of solid components including these excipients. [0017] If carbonate and organic acid are reactive under normal conditions, in the case of tablets, for example, a multi-layered tablet containing sodium bicarbonate in the first layer and citric acid in the third layer and blended in a non-contact manner. In the case of tablets, granules, or powders, for example, sodium bicarbonate and citric acid should be packaged separately or dispersed with a chemically inert substance such as crystalline cellulose to minimize the chance of contact between the two. This makes it possible to prevent the reaction from progressing in the preparation. [0018] According to the present invention, it is effective in masking pharmaceutical preparations containing components having an unpleasant taste such as bitterness, and is suitable for improving the feeling of taking internal medicines. moreover,
The method of the present invention may be employed not only to mask bitterness but also to improve the palatability of compositions containing taste-discomforting ingredients, and this method can be widely applied not only to pharmaceuticals but also to food and other fields. can do. [Example] Example 1 One part of caffeine was taken as a bitter component, and xylitol,
The bitterness masking effect was evaluated for compositions in which sodium bicarbonate, ascorbic acid, citric acid, and tartaric acid were added at various mixing ratios and the total amount was made up to 100 parts with lactose (see Table 1). [0020] The effect was evaluated by a sensory test conducted by a panel of 27 people, and the bitterness was evaluated as - if the bitterness was not felt within 5 minutes after the start of dissolution in the oral cavity, ± if it was hardly felt, + if it was weak, and ++ if it was strong. The results are shown in Table 1 below. [Table 1]



Comparison example
Example
No. 1 2 3 4 5
6 7 1 2 3 4 5 Composition (parts): Caffeine 0 0
1 1 1 1 1 1
1 1 1 1 xylitol
0 50 50 30 0
0 0 0 30 30 30
30 Sodium hydrogen carbonate 5 0
0 0 0 5 0 5
5 5 5 5 Ascorbic acid
3 0 0 0 3
0 0 3 3 8 0
0 citric acid 3
0 0 0 3 0 0
3 3 0 8 0 Tartaric acid
3 0 0
0 3 0 0 3 3
0 0 8 Rating (people): -27
27 2 0 0 0 0
20 24 23 20 22 ±
0 0 18
7 2 0 0 7
2 4 5 4 +
0 0 7 19
16 1 0 0 1 0
2 1 ++
0 0 0 1 9 26
27 0 0 0 0 0
Example 2 Comparative Example 7 of Example 1 was used as Sample A, Comparative Example 3 was used as Sample B,
Example 1 was designated as Sample C, and the bitterness sensitivity of these compositions was 6.
Comparisons were made by a human panel. [0023] Each panelist selects combinations (A, B), (A,
C) and (B, C) were evaluated once each using a 7-point scale. The results are shown in Table 2. Analysis of the paired comparison method revealed that bitterness masking was better in the order of C, B, and A, and the difference was significant (p<0.05). [Table 2] Panelist O1 O2 O
3 O4 O5 O6 A
B -2 -1 -1
-3 -3 -2 A
C -3 -3 -3
-3 -3 -3 B C
-2 -2 -1 -
20-3 [0025] Examples of formulations according to the present invention are shown below. Regarding the bitter taste masking effect, ease of administration, and palatability, each of these Examples was extremely good compared to all the comparative examples shown below. Example 3 Dimenhydrinate
5.5 (parts) Anhydrous caffeine
4.0 Sodium Bicarbonate 6.
0 ascorbic acid
12.0 xylitol
50.0 Hydroxypropyl cellulose 2.0 Crystalline cellulose
20.0 Magnesium stearate
0.5 fragrance
Trace amount 00
27] Tablets are prepared using the above-mentioned amount in a conventional manner and used as an antidepressant. Comparative Example 1 is an example in which sodium bicarbonate and ascorbic acid among the above ingredients are replaced with lactose. Example 4 Chlorpheniramine maleate 0
．． 2 (Part) Diprophylline
3.0 Pyridoxine hydrochloride
0.5 sodium bicarbonate
8.0 citric acid
4.0 Succinic acid

4.0 sucrose
60.0 Hydroxypropyl cellulose 3.0 Lactose

13.0 corn starch
4.3 [0029] Tablets are prepared using the above-mentioned amount in a conventional manner and used as an antidepressant. In addition, among the above ingredients, sodium bicarbonate, citric acid,
Comparative Example 2 is one in which succinic acid is replaced with lactose. Example 5 Caffeine
1.5 (parts) diphenhydramine salicylate 2.3 l-menthol
0.0
Sodium bicarbonate
8.0 malic acid
5.0 tartaric acid

5.0 mannitol
40.0 Saccharin

0.68 crystalline cellulose
30.0 lactose

7.0 Magnesium Stearate
0.5 [0031] Tablets are prepared in the above-mentioned amount by a conventional method and used as an antidepressant. Comparative Example 3 is an example in which sodium bicarbonate, malic acid, and tartaric acid among the above ingredients are replaced with lactose. Example 6 Diphenhydramine salicylate 4
．． 0 (parts) diprophylline
2.5 Sodium bicarbonate
5.0 Succinic acid
6.0 malic acid
8.0 xylitol
30.0 saccharin
1.0 Hydroxypropylcellulose 3.5 Lactose

25.0 corn starch
15.0 [0033] Granules are prepared in the above-mentioned amount by a conventional method and used as an antidepressant. Comparative Example 4 is an example in which sodium bicarbonate, succinic acid, and malic acid among the above ingredients are replaced with lactose. Example 7 Dextromethorphan phenolphthalin salt
2.0 (parts) Guaifenesin
5.
3 Chlorhexidine hydrochloride
0.3 Sodium bicarbonate
5.0 Ascorbic acid

4.0 Tartaric acid

4.0 Mannitol
30.
4 Xylitol
40.0
talc
3.3 Magnesium stearate
1.5 Corn starch

4.2 Flavorings
Trace amount [0035] A lozenge is prepared in the above-mentioned amount by a conventional method and is used as an antitussive and expectorant. Comparative Example 5 is an example in which sodium bicarbonate, ascorbic acid, and tartaric acid among the above ingredients were replaced with lactose. Example 8 Dihydrocodeine phosphate
0.5 (part) dl-methylephedrine hydrochloride
1.4 Noscapine
1.1 Lysozyme chloride
1.1 Chlorpheniramine maleate
0.2 Potassium guaiacol sulfonate
4.0 Sodium bicarbonate
8.0 citric acid
14
．． 0 sorbitol
30.7 Hydroxypropyl cellulose 3.0 Lactose
1
8.0 corn starch
18.0 [0037] Granules are prepared in the above-mentioned amount by a conventional method, and are used as an antitussive and expectorant. Furthermore, Comparative Example 6 was prepared by replacing sodium bicarbonate and citric acid with lactose among the above ingredients.

Claims (1)

[Claims] 1. An oral solid preparation for a substance having an unpleasant taste, which contains a foaming agent that foams when dissolved in the oral cavity.