Solid Dosage Forms

Abstract

To provide a solid preparation in which unpleasant taste of magnesium salt or bisacodyl of a saline laxative is improved.SOLUTION: It is found that unpleasant taste can be improved and furthermore, grainy feeling in an oral cavity can be improved when Plantago ovata being a swelling laxative is blended. Specifically, the present invention is a solid preparation that contains (A) at least one kind selected from the group consisting of magnesium salt of a saline laxative and bisacodyl, and (B) Plantago ovata, where in the case where the component (A) is magnesium oxide, a content of the component (B) is 12 to 20 pts.mass for 1 pt.mass of the magnesium oxide (A), in the case where the component (A) is magnesium hydroxide, a content of the component (B) is 2 to 20 pts.mass for 1 pt.mass of the magnesium hydroxide (A), and in the case where the component (A) is magnesium sulfate, a content of the component (B) is 0.1 to 5 pts.mass for 1 pt.mass of the magnesium sulfate (A).SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to solid preparations and has excellent palatability containing an active ingredient having an unpleasant taste. It relates to preparations.

Background Art

[0002] Saline cathartics such as magnesium oxide, magnesium hydroxide, magnesium sulfate, and magnesium carbonate suppress water absorption in the large intestine and cause the feces in the intestine to contain water and become bulky and soft, which has an effect of promoting defecation and is widely used as a laxative with few side effects. Also, since it has an antacid effect in the pharmaceutical field, it is widely used as an antacid and a gastric mucosa protecting component in oral medications such as gastrointestinal drugs, laxatives, and cold medicines.

[0003] Bisacodyl directly acts on the large intestine mucosa and is used as a laxative that promotes peristaltic movement of the intestine and promotes defecation, and is mainly widely used by oral administration (Patent Document 1). In oral administration, in order to avoid the reduction of the effect by being decomposed in the stomach or causing unnecessary irritation to the gastric mucosa, many enteric preparations in which tablets are coated so as to dissolve in the intestine are used. Also, in the case of enteric preparations, since there is a risk that bisacodyl may dissolve in the stomach, it is recommended to avoid taking gastrointestinal drugs containing an antacid component or drinking milk within 1 hour before and after taking the medicine.

[0004] While these active ingredients are widely used, it has been reported that they have specific unpleasant tastes (bitter taste, salty taste, etc.) [[ID=…]] (Patent Documents 2 and 3).

[0005] The unpleasant taste of oral dosage forms impairs the taking feeling and causes a decrease in medication compliance (Patent Document 4). In particular, powders, granules, orally disintegrating tablets, chewable tablets, plain tablets, etc. In the case of oral medications in this dosage form, there is more contact between the oral medication's ingredients and the tongue, which can lead to an unpleasant taste and discomfort when taking the medication. The deterioration will become significant.

[0006] To date, we have helped people suppress the unpleasant taste of magnesium oxide, magnesium hydroxide, and bisacodyl. Several methods have been reported. For example, the unpleasant taste of magnesium oxide and magnesium hydroxide. As a method of suppression, combining it with stevia improves the feeling of taking it, the flavor, and the aftertaste. It has been reported that an oral composition was obtained (Patent Document 5). Also, in Patent Document 2 These are basic inorganic salts such as magnesium oxide, magnesium hydroxide, and magnesium carbonate. As a method to suppress unpleasant taste, combining lactate and sucralose improves the taste and mouthfeel. It has been reported that an oral composition with improved taste and aftertaste has been obtained. In this context, a coating method containing a specific excipient has been reported as a method for masking unpleasant tastes. It has been reported (Patent Document 6). However, these methods involve specific sweeteners or specific excipients. Because its use is essential and requires a coating process, raw material costs will increase. This will extend the process time, and further consideration is needed. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Japanese Patent Publication No. 2007-55969 [Patent Document 2] Japanese Patent Publication No. 2016-204353 [Patent Document 3] Japanese Patent Publication No. 2015-42634 [Patent Document 4] Japanese Patent Publication No. 2011-6481 [Patent Document 5] Japanese Patent Application Laid-Open No. 9-52827 [Patent Document 6] Japanese Patent Application Laid-Open No. 2010-120956 [Summary of the Invention] [Problems to be Solved by the Invention]

[0008] An object of the present invention is to provide a solid preparation in which the unpleasant taste of magnesium salts or bisacodyl as saline laxatives is improved. [Means for Solving the Problems]

[0009] As a result of various studies to solve the above problems, the present inventors have surprisingly found that when Plantago ovata, a swelling laxative, is blended, the unpleasant taste can be improved, and furthermore, the roughness in the oral cavity can also be improved, and the acceptability can be further improved, leading to the completion of the present invention.

[0010] That is, the present invention is: (1) (A) At least one selected from the group consisting of magnesium salts of saline laxatives and bisacodyl, and (B) Plantago ovata, and when component (A) is magnesium oxide, the content of component (B) is 10 to 20 parts by mass with respect to 1 part by mass of (A) magnesium oxide, and when component (A) is magnesium hydroxide, the content of component (B) is 2 to 20 parts by mass with respect to 1 part by mass of (A) magnesium hydroxide, and when component (A) is magnesium sulfate, the content of component (B) is 0.1 to 5 parts by mass with respect to 1 part by mass of (A) magnesium sulfate, and a solid preparation characterized by the above, (2) (A) The magnesium salt of the saline laxative is magnesium oxide, magnesium hydroxide, sulfuric acid At least one selected from the group consisting of magnesium and magnesium carbonate (1 ) The solid preparation according to (3) When component (A) is magnesium carbonate, the content of component (B) is (A) magnesium carbonate It is 0.1 to 10 parts by mass with respect to 1 part by mass of um, and is characterized in that it is described in (1) or (2) The solid preparation described, (4) The content of (B) Plantago ovata is 10 to 95% by mass based on the total solid preparation The solid preparation according to any one of (1) to (3), (5) The content of (A) magnesium oxide is 1 to 9% by mass based on the total solid preparation, (The solid preparation according to any one of (1), (2) or (4), (6) The content of (A) magnesium hydroxide is 5 to 40% by mass based on the total solid preparation The solid preparation according to any one of (1), (2) or (4), (7) The solid preparation according to any one of (1) to (6) further containing an organic acid, (8) The dosage form is an orally disintegrating tablet, chewable tablet, plain tablet, granule, or powder (1) to (7 ) The solid preparation according to any one of (9) (B) Plantago ovata is Plantago ovata seeds or Plantago ovata The solid preparation according to any one of (1) to (8), which is the seed coat, is.

Effect of the Invention

[0011] According to the present invention, the unpleasant taste of the magnesium salt or bisacodyl of the saline laxative is suppressed, and the feeling of taking is good, and a solid preparation can be provided.

Mode for Carrying Out the Invention

[0012] As the magnesium salt of the saline laxative in the present invention, magnesium oxide, magnesium hydroxide Examples include calcium, magnesium carbonate, and magnesium sulfate.

[0013] The magnesium oxide used in this invention conforms to the Japanese Pharmacopoeia or food additives. It is magnesium, which can be manufactured by known methods, or commercially available magnesium can be used. The magnesium oxide content of the present invention is, from the viewpoint of palatability, relative to the total solid preparation of the present invention. Therefore, 1 to 9% by mass is preferred, and 5 to 9% by mass is more preferred.

[0014] The magnesium hydroxide used in this invention conforms to the Japanese Pharmacopoeia Standards for Non-Official Drugs or Food Additives. This is magnesium hydroxide, which can be manufactured by known methods, or commercially available magnesium hydroxide can be used. This can be done. The magnesium hydroxide content of the present invention is determined from the viewpoint of palatability, as is the solid product of the present invention. Preferably 1 to 50% by mass of the total agent, more preferably 5 to 40% by mass, and 5 to 33% by mass. Mass percent is even more preferable.

[0015] The magnesium carbonate used in this invention conforms to the Japanese Pharmacopoeia or food additives. It is magnesium, which can be manufactured by known methods, or commercially available magnesium can be used. The magnesium carbonate content of the present invention is, from the viewpoint of palatability, relative to the total amount of the solid preparation of the present invention. Therefore, 10 to 90% by mass is preferred, and 12 to 86% by mass is more preferred.

[0016] The magnesium sulfate used in this invention conforms to the Japanese Pharmacopoeia or food additives. It is magnesium, which can be manufactured by known methods, or commercially available magnesium can be used. The magnesium sulfate content of the present invention is, from the viewpoint of palatability, relative to the total amount of the solid preparation of the present invention. Therefore, 10 to 90% by mass is preferred, and 20 to 86% by mass is more preferred.

[0017] The bisacodyl used in this invention is bisacodyl in accordance with the Japanese Pharmacopoeia, and is obtained by known methods. It can be manufactured in-house, or commercially available products can be used. The bisacodyl content of the present invention is From the viewpoint of palatability, 0.0001 to 1% by mass of the solid dosage form of the present invention is preferred. A range of 0.0001 to 0.85% by mass is more preferable.

[0018] In this invention, the Plantago ovata used is not limited to seeds, stems, leaves, roots, etc., but Seeds containing a large amount of swelling laxative (psyllium gum) are preferred. Also, when using seeds... For the mixture, either the whole seed or only the seed coat may be used, but the seed coat or seed coat powder is more preferable. Plantago ovata absorbs water and swells, thereby physically stimulating the intestinal wall. This method produces a laxative effect by increasing stool volume. The daily dose is preferably 1050-10500 mg, and 2100-10500 mg. g is more preferable. The amount of Plantago ovata in this invention is more preferable from the viewpoint of exerting a laxative effect. Therefore, 10 to 95% by mass of the total solid formulation of the present invention is preferred. In the present invention, when magnesium oxide and Plantago ovata are combined, Plantago... The amount of psyllium is preferably 60-95% by mass, and more preferably 84-92% by mass. When combining magnesium oxide and psyllium husk, the amount of psyllium husk should be... , 40-95% by mass is preferred, 50-94% by mass is more preferred, and 55-92% by mass is Even more preferable. When combining magnesium carbonate and Plantago ovata, Plantago... The amount of psyllium is preferably 5 to 85% by mass, and more preferably 10 to 85% by mass. When combining magnesium and psyllium husk, the amount of psyllium husk should be 5 ~85% by mass is preferred, and 10~77% by mass is preferred. When bisacodyl is included, The amount of Lantago ovata added is preferably 75-90% by mass.

[0019] Furthermore, in the present invention, when magnesium oxide and Plantago ovata are combined, The amount of psyllium husk included is used to suppress the unpleasant taste of magnesium oxide or to improve roughness in the mouth. From this perspective, the amount is 10 to 20 parts by mass per 1 part by mass of magnesium oxide, and more preferably The amount is 12 to 20 parts by mass, and more preferably 12 to 17.5 parts by mass. In the solid dosage form of the present invention, when magnesium hydroxide and Plantago ovata are combined. The amount of Plantago ovata included is used to suppress the unpleasant taste of magnesium hydroxide and in the oral cavity. From the standpoint of improving roughness, the ratio is 2 to 20 parts by mass per 1 part by mass of magnesium hydroxide, which is preferable. The amount is 2 to 16.7 parts by mass, more preferably 3.3 to 16.7 parts by mass. In the solid dosage form of the present invention, when magnesium sulfate and Plantago ovata are combined, The amount of Lantago ovata included is for suppressing the unpleasant taste of magnesium sulfate and for reducing grittiness in the mouth. From the viewpoint of improvement, the amount is preferably 0.1 to 5 parts by mass per 1 part by mass of magnesium sulfate. This is 0.14 to 3.5 parts by mass. In the solid formulation of the present invention, when magnesium carbonate and Plantago ovata are combined, The amount of Lantago ovata included is for suppressing the unpleasant taste of magnesium carbonate and for reducing grittiness in the mouth. From the standpoint of improvement, the ratio is 0.1 to 10 parts by mass per 1 part by mass of magnesium carbonate, which is preferable. The amount is 0.1 to 7 parts by mass.

[0020] Furthermore, in the present invention, when bisacodyl and Plantago ovata are combined, Plantago The amount of psyllium used is preferably 105 to 525 parts by mass per 1 part by mass of bisacodyl.

[0021] Organic acids can be used as edible acids in the solid formulation of the present invention. For example, Econic acid, succinic acid, ascorbic acid, acetic acid, gluconic acid, malic acid, tartaric acid, fumaric acid, Examples include organic acids such as adipic acid, which can be used alone or in combination of two or more. This can be done. Among them, citric acid, malic acid, and tartaric acid are preferred. The content of these organic acids is Preferably, 1 to 70% by mass, and more preferably 1 to 50% by mass, relative to the total solid dosage form of the present invention. More preferably 1 to 30% by mass, and most preferably 2.4 to 27% by mass. The solid dosage form of the present invention is not particularly limited, but may include, for example, pharmaceuticals, quasi-drugs, and foods. Examples include pharmaceuticals and quasi-drugs.

[0022] The formulation of the present invention may contain various commonly used additives, as long as they do not impair the effects of the present invention. It may contain such additives, for example, excipients, disintegrants, binders, and fluidizers. Agents, lubricants, acidulants, foaming agents, sweeteners, flavoring agents, fragrances, colorants, surfactants, plasticizers, etc. While these can be listed, from the perspective of unpleasant taste, it is more preferable to include sweeteners and flavoring agents.

[0023] The dosage forms of this preparation include, for example, tablets, granules, and powders. These are dissolved in water. The tablets of this invention may be solid preparations for oral administration. This includes the prescribed orally disintegrating tablets, chewable tablets, uncoated tablets, effervescent tablets, dispersible tablets, and dissolvable tablets. ru.

[0024] Furthermore, even if the solid dosage form of the present invention is a solid dosage form that is dissolved in water before administration, The unpleasant taste of the magnesium salt in the preparation is improved. Furthermore, the solid preparation of the present invention can be an orally disintegrating tablet or Chewable tablets are formulations that can be taken directly without water, or they can be placed in the mouth and then taken with water. In the case of swallowed formulations, the roughness in the oral cavity can also be improved.

[0025] The tablets of this invention can be provided with score lines, marks for improved identification, and engravings. Furthermore, the tablets of this preparation may be round tablets or irregularly shaped tablets. Therefore, from the perspective of taste perception, the test will be conducted using orally disintegrating tablets, chewable tablets, uncoated tablets, granules, and powders. Its significance is greater. The tablets of the present invention can be manufactured by conventional methods for manufacturing tablets. In other words, this preparation is made by mixing the active pharmaceutical ingredient with the aforementioned additives using a suitable mixing machine such as a mixer. After mixing to produce a tablet mixture, the mixture is compressed directly into tablets, or granules are used. It can be manufactured by methods such as compression tableting. The method for manufacturing granules is dry granulation (S It can be manufactured by the lag method, roller compactor method, or wet granulation method, and granulation equipment These include roller compactors, agitation granulation, fluid bed granulation, extrusion granulation, and rolling granulation. The product can be manufactured by granulation, spray granulation, etc. The tablet mixture or granules of the mixture are compressed into tablets. Machines that can be used include single-shot tablet presses and rotary tablet presses. [Examples]

[0026] The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to these examples. This is not limited to examples, etc.

[0027] (Preparation of pharmaceutical products) (Examples 1-12, Comparative Examples 1-8) After weighing each raw material component according to the formulations listed in Tables 1 and 2, they were uniformly mixed. The mixture and an appropriate amount A mixture of water and ethanol was added and kneaded in a mortar, then granulated and thoroughly dried. The mixture was passed through a sieve (mesh size 500 μm) to obtain granules, which were then divided into three packets.

[0028] <Drug efficacy test> Each formulation in Examples 1-12 and Comparative Examples 1-8 was subjected to sensory evaluation by two expert panel members. They did that. There are two ways to take the medication: (Method 1) Place one packet of the preparation in your mouth and swallow it with water, and (Method 2) Take it with water There are two methods of administration: dissolving it in water and then taking it (method 2), and taking it requires one glass of water. Water was used. For method 1 of administration, unpleasant taste and grittiness were evaluated, and for method 2 of administration, unpleasant taste was evaluated. An evaluation was conducted. Regarding unpleasant taste and grittiness, the evaluation was carried out according to the following criteria: The average value of the expert panel was calculated.

[0029] <Unpleasant taste> 0: No unpleasant taste. 1: Slightly unpleasant taste 2: Slightly unpleasant taste 3: Feeling an unpleasant taste 4: Experiencing a strong unpleasant taste. <roughness> 0: No roughness felt 1: Slightly rough texture 2: Slightly rough texture 3: Feeling rough 4: I feel a strong roughness.

[0030] The results are shown in Table 1.

[0031] [Table 1]

[0032] [Table 2]

[0033] As shown in Tables 1-2, Plantago ovata is mixed with 1 part by mass of magnesium hydroxide. Incompatible formulations and formulations containing 1 part by mass of Plantago ovata exhibit an unpleasant taste and grittiness. This was observed (Comparative Examples 1-3). In contrast, plan was used for 1 part by mass of magnesium hydroxide. The present invention, which contains 2 parts by mass of Tago ovata, reduces unpleasant taste and grittiness. (Examples 3 and 4). Furthermore, when the formulation was dissolved in water and drunk, no unpleasant taste was detected at all. Examples 3 and 4). Plantago ovata is added in an amount of 25 parts by mass per 1 part by mass of magnesium hydroxide. When the dosage was increased to 0.4 parts by mass, the unpleasant taste improved, but a gritty texture developed. Furthermore, when taken... Sometimes the formulation would clump together in the mouth, making it impossible to swallow (Comparative Example 4).

[0034] Furthermore, as shown in Table 1, bisacodyl also contains Plantago ovata. The unpleasant taste was further improved (Examples 5 and 6).

[0035] Regarding magnesium oxide, the grittiness level was 2 or less in all formulations, however The pleasant taste tended to decrease with increasing amounts of Plantago ovata. A formulation containing 3.5 parts by mass of Plantago ovata per 1 part by mass of um, and a formulation containing 9 parts by mass of Plantago ovata. Both formulations produced an unpleasant taste. On the other hand, when 1 part by mass of magnesium oxide was used, plant Adding 10 parts by mass or more of psyllium husk improved the unpleasant taste (Examples 7-9, Comparative Example 6-9) 7).

[0036] [Table 3] As shown in Table 3, 0.07 parts of Plantago ovata per 1 part by mass of magnesium sulfate In formulations containing the specified amount, the unpleasant taste could not be suppressed (Comparative Example 8). The blending ratio of Plantago ovata to 1 part by mass of magnesium sulfate is 0.14 parts by mass or more. The blending ratio of Plantago ovata to 1 part by mass of magnesium carbonate is 0.1 parts by mass or more. The present invention's products had reduced unpleasant taste and no grittiness (Examples 10-13).

[0037] (Example of formulation) (Examples of formulations 1, 2, 4, 5) The following ingredients and quantities were used in 12 tablets, and the product was manufactured in accordance with the general rules for Japanese Pharmacopoeia preparations. (Formulation examples 3, 6) The following ingredients and quantities were used in 6 packets, and the product was manufactured in accordance with the general guidelines for Japanese Pharmacopoeia preparations. (Formulation examples 7, 8) The following ingredients and quantities were used in 24 tablets, and the product was manufactured in accordance with the general rules for Japanese Pharmacopoeia preparations.

[0038] Examples of formulations of the present invention are shown in Table 4 below.

[0039] [Table 4] [Industrial applicability]

[0040] According to the present invention, a solid laxative is available that improves the unpleasant taste of magnesium salts or bisacodyl, which are saline laxatives. We can provide the agent.

Claims

1. An oral solid preparation comprising (A) bisacodyl and (B) Plantago ovata, wherein the content of component (B) is 105 to 525 parts by mass per 1 part by mass of (A), and the dosage form is an orally disintegrating tablet, a chewable tablet, a plain tablet, granules, or a powder.

2. The oral solid preparation according to claim 1, further comprising an organic acid.

3. (B) The oral solid formulation according to claim 1 or 2, wherein Plantago ovata is Plantago ovata seeds or Plantago ovata seed coats.

4. A method for producing an oral solid preparation, comprising (A) bisacodyl and (B) Plantago ovata, wherein the content of component (B) is 105 to 525 parts by mass per 1 part by mass of (A), and the dosage form is an orally disintegrating tablet, a chewable tablet, a plain tablet, granules, or a powder, the method comprising the step of mixing (A) and (B).

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