JP2020203854A - Method for producing tablet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a tablet having roughness suitable for removing tongue coating and excellent in manufacturability and tablet characteristics.
A method for producing a tablet containing sorbitol and erythritol, which comprises mixing sorbitol granules and erythritol granules and tableting.
[Selection diagram] None

Description

The present invention relates to a method for producing a tablet containing sorbitol and erythritol.

Halitosis refers to having an unpleasant odor emanating from the oral cavity and can affect interpersonal relationships. Tongue coating is one of the major causes of bad breath.

Tablets with roughness are known for the purpose of removing tongue coating, and this tablet is a mixture of high-solubility sugars such as maltitol, sorbitol, and erythritol and low-solubility sugars such as palatinit and mannitol. It can be obtained by directly tableting (Patent Document 1).

Further, as a solid preparation containing two or more kinds of sugars, which is not intended for removing tongue moss, a troche agent containing sugars selected from D-sorbitol, xylitol and reduced maltose (Patent Document 2), mannitol and / Alternatively, a solid preparation composition containing lactose and sorbitol powder (Patent Document 3), two or more sugar alcohols selected from erythritol, xylitol, D-sorbitol, D-mannitol, powdered reduced maltose water candy and martitol, etc. Solid preparations containing (Patent Document 4) and the like are known.
Further, a method for producing erythritol-sorbitol mixed granules is also known, which comprises granulating erythritol and sorbitol at a mass ratio of 99: 1 to 80:20 by stirring and mixing them at high speed while spraying hydroalcohol. (Patent Document 5).

However, in a method for producing a tablet containing sorbitol and erythritol, a method characterized by mixing granules of both components and tableting has not been known so far.

International Publication No. 2007/026755 JP-A-6-72860 Japanese Patent Application Laid-Open No. 5-310558 Japanese Patent Application Laid-Open No. 2008-214325 JP-A-2006-335686

The present invention has a roughness suitable for removing tongue coating, which is the main cause of bad breath, has an excellent feeling of ingestion, does not give a feeling of powderiness, and further improves the manufacturability such as no cracking or chipping of tablets. It is an object of the present invention to provide a tablet having excellent characteristics such as hardness and disintegration time and a method for producing the same.

As a result of diligent studies, the present inventors have found that the above problems can be solved by mixing sorbitol granules and erythritol granules and tableting them, and have completed the present invention.
That is, the present invention includes the following aspects.
[1] A method for producing a tablet containing sorbitol and erythritol.
A method for producing a tablet, which comprises mixing sorbitol granules and erythritol granules and tableting them.
[2] The production method according to [1], wherein 60% by weight to 90% by weight of sorbitol and 10% by weight to 40% by weight of erythritol are blended with respect to the entire tablet.
[3] The production method according to [1] or [2], wherein modified starch is added.
[4] The production method according to any one of [1] to [3], wherein a halitosis preventing or removing component is added.
[5] The production method according to any one of [1] to [4], wherein the orally disintegrating time of the tablet is 30 seconds to 15 minutes.
[6] The production method according to any one of [1] to [5], wherein the tablet is for preventing or removing bad breath.

According to the present invention, by imparting an appropriate degree of roughness to a tablet, removal of tongue coating, which is the main cause of bad breath, can be expected, and a tablet having an excellent feeling of administration without feeling powdery at the time of administration is provided. be able to.
Further, according to the present invention, it is intended to provide a tablet having a disintegration time suitable for the purpose of removing tongue coating and having excellent tablet hardness and tablet abrasion degree to reduce cracking and chipping of tablets in a manufacturing process and a filling process. Can be done.

The method for producing a tablet containing sorbitol and erythritol of the present invention is characterized in that sorbitol granules and erythritol granules are mixed and tableted.

Examples of the "tablet" (tablet) in the present invention include gum agents, sublingual tablets, lozenges, drops, buccal tablets, adherent tablets, orally disintegrating tablets, chewable tablets, effervescent tablets, dispersion tablets, dissolving tablets and the like. However, a troche agent is preferable.

Since the tablet in the present invention can remove tongue coating, which is one of the main causes of halitosis, it can be used for prevention or removal of halitosis. The term "tongue coating" as used herein refers to white moss-like material attached to the tongue, which includes bacteria, food residue, and mucosal residue.

The "sorbitol granule" in the present invention means sorbitol in the form of granules. The sorbitol is not particularly limited, and examples thereof include known sorbitol published in the Japanese Pharmacopoeia. In addition, the sorbitol granules may contain additives other than sorbitol (for example, excipients, binders, disintegrants, fluidizers, flavoring agents, etc.) as long as the effects of the present invention are produced. ..
Excipients include, for example, processed starch, D-mannitol, xylitol, martitol, trehalose, lactose, glucose, fructose, sucrose, powdered reduced maltose water candy, isomalt, reduced palatinose, crystalline cellulose, microcrystalline cellulose, powdered cellulose. , Ethyl cellulose, dextrin, β-cyclodextrin, carmellose sodium, corn starch, light anhydrous silicic acid, hydrous silicon dioxide, silicon dioxide, calcium silicate, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, magnesium oxide, titanium oxide, Examples thereof include calcium lactate, calcium sulfate, magnesium aluminometasilicate, synthetic hydrotalcite, talc, and kaolin.
Examples of the binder include hydroxypropyl cellulose, hydroxypropyl methyl cellulose (hypromellose), polyvinylpyrrolidone, polyvinyl alcohol, copolyvidone, gum arabic powder, methyl cellulose, low-substituted hydroxypropyl cellulose, carmellose sodium, dextrinpurulan, gum arabic, and canten. , Gelatin, tragant, sodium alginate and the like, preferably hydroxypropyl cellulose disintegrants include, for example, carmellose, carmellose calcium, carboxymethyl starch sodium, carboxymethyl cellulose, carboxymethyl cellulose calcium, croscarmellose sodium, etc. Examples thereof include crospovidone, low-substituted hydroxypropyl cellulose (L-HPC), hydroxypropyl starch and the like, and crospovidone is preferable.
Examples of the fluidizing agent include light anhydrous silicic acid, talc, hydrous silicon dioxide, synthetic aluminum silicate, magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate and the like.
Examples of the flavoring agent include natural or synthetic sweeteners such as sucrose, sucralose, xylitol and aspartame, and refreshing agents such as peppermint oil, mint flavor, peppermint powder, dl-menthol and l-menthol.
The particle size of the sorbitol granules is not particularly limited as long as the above-mentioned effect of the present invention is produced, and examples thereof include those that have passed through a 16-mesh sieve and remain in a 100-mesh sieve, preferably passing through a 30-mesh sieve and 100. Examples include those remaining on the mesh sieve. Here, the sieving and sieving method can follow the Japanese Pharmacopoeia.
Further, the sorbitol granules preferably have a bulk density of 0.3 to 0.7 g / ml.
As the sorbitol granules, for example, commercially available products such as NEOSORB XTAB, NEOSORB P (Rocket Japan), and Parteck SI (Merck) may be used, and the granules are manufactured according to the general method of granules described in the publication. You may. For example, known methods such as extrusion granulation, rolling granulation, stirring granulation, fluidized bed granulation, spray drying granulation, crush granulation, and melt granulation can be used. For example, the Granulation Handbook (Japan) Powder Industry Technology Association, Ohm), Formulation design for orally administered preparations (edited by Professor Mitsuru Hashida, Graduate School of Pharmaceutical Sciences, Kyoto University, Yakuhin Jihosha), Compression molding technology for powders (powder engineering / preparation and particle design) Subcommittee edition, Nikkan Kogyo Shimbun), Formulation Machinery Technology Handbook (2nd edition, 20th Anniversary Publication Editorial Committee Edition of Formulation Machinery Technology Study Group, Formulation Machinery Technology Study Group) Can be used.

"Erythritol granules" in the present invention means erythritol in the form of granules. The erythritol is not particularly limited, and examples thereof include known erythritol published in the Japanese Pharmacopoeia. In addition, the erythritol granules may contain the same additives as those other than sorbitol as long as the effects of the present invention are produced.
The particle size of the erythritol granules is not particularly limited as long as the effect of the present invention is produced, but examples thereof include those that have passed through a 16-mesh sieve and remain in a 100-mesh sieve, preferably passing through a 30-mesh sieve. , Those remaining on the 100 mesh sieve can be mentioned. Here, the sieving and sieving method can follow the Japanese Pharmacopoeia.
Further, the erythritol granules preferably have a bulk density of 0.3 to 0.7 g / ml.
As the erythritol granules, for example, a commercially available product such as erythritol granules (Micro Foods Japan) may be used, or the granules may be produced according to the general method of granules described in publications. For example, known methods such as extrusion granulation, rolling granulation, stirring granulation, fluidized bed granulation, spray drying granulation, crush granulation, and melt granulation can be used, and for example, the granulation exemplified above can be used. The methods described in publications such as the Grain Handbook can be used.

The weight ratio of sorbitol to erythritol in the whole tablet of the present invention is not particularly limited as long as the above-mentioned effect of the present invention occurs. For example, sorbitol is 30 to 95% by weight and erythritol is 5 to 70% by weight based on the whole tablet. Sorbitol can be blended in a weight ratio of 60 to 90% by weight and erythritol can be blended in a weight ratio of 10 to 40% by weight.

The tablets in the present invention may contain, in addition to the sorbitol granules and the erythritol granules, pharmaceutically acceptable additives commonly used in the field of formulation technology, as long as the effects of the present invention are not impaired. Examples of such additives include excipients, binders, disintegrants, flavoring agents, lubricants, fluidizing agents, colorants, pH regulators, surfactants, stabilizers, fragrances and the like. These additives are used in conventional amounts in the field of formulation technology.

Examples of excipients include those exemplified as additives other than the above-mentioned sorbitol, but modified starch is preferably included. By adding modified starch, it is possible to reduce the equilibrium relative humidity (ERH) in the tablets of the present invention containing a large amount of water-soluble excipients, thereby preventing the tablet from being deteriorated in stability. can do. The ERH of the tablet in the present invention is, for example, about 50% or less, preferably about 40% or less, and more preferably about 20% or more and 30% or less.
Examples of starch that constitutes (or is a raw material component of processed starch) of processed starch include rice, mochigome, corn, mochi corn, amiro corn, morokoshi, wheat, barley, sweet potato, rhyokuto, potato, lily, katakuri, and tulip. , Canna, pea, perilla pea, chestnut, kudzu, yamanoimo, corn, corn, green bean, sago, tapioca (cassaba), warabi, hass, hiss and other natural starches, aged starch, cross-linked starch and the like. These starches can be used alone or in combination of two or more. Of these starches, they are often at least one starch selected from potatoes, wheat, corn, rice, tapioca, and citrus. In particular, as the starch, natural starch such as potato starch is preferable.
Examples of starch processing include etherification such as cross-linking, phosphorylation, acetylation, and hydroxypropylation, oxidation, pregelatinization, and combinations thereof, and pregelatinization is preferable.
Pregelatinized starch is starch that has been pregelatinized by heating it with water, including whole starch pregelatinized (pregelatinized starch) and partially pregelatinized starch (partially pregelatinized starch). ) Both are included. Specific examples thereof include those described in "Pharmaceutical Additives Dictionary 2016" edited by the Japan Pharmaceutical Additives Association, and examples of commercially available products include partially pregelatinized starch PCS ^(R) and pregelatinized starch PD-. 1. Pregelatinized starch WB-1 (both are Asahi Kasei Corporation) and the like.
The ratio of the modified starch in the entire tablet of the present invention is not particularly limited as long as the above-mentioned effect of the present invention is produced, but for example, 1 to 20% by weight of the modified starch can be blended with respect to the entire tablet, preferably. It can be blended in an amount of 3 to 10% by weight.

Examples of the binder, disintegrant, fluidizing agent, and flavoring agent include those exemplified as additives other than the above-mentioned sorbitol. By including the binder, sorbitol or erythritol can be granulated together with other components. In addition, the inclusion of a disintegrant can prevent delay in disintegration and provide an appropriate disintegration time in the oral cavity.

Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, and the like, and magnesium stearate is preferable. By containing a lubricant, it is possible to prevent creaking during tableting.

Examples of the colorant include riboflavin, titanium oxide, iron sesquioxide, yellow iron sesquioxide and the like.
Examples of the pH adjusting agent include citrate, phosphate, carbonate, tartrate, fumarate, acetate, amino acid salt and the like.
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 fragrance include L-menthol, peppermint oil, lemon oil and vanillin.

The tablets of the present invention may further contain halitosis-preventing or removing ingredients. By using these halitosis preventive or removing components, it is possible to chemically prevent or remove halitosis in addition to physically removing tongue coating due to roughness at the time of administration.

Halitosis prevention or removal components include, for example, components that suppress the sterilization or growth of oral bacteria, or volatile sulfides (VSC; hydrogen sulfide) that are produced by the metabolism of anaerobic bacteria in the oral cavity and cause halitosis. , Methyl mercaptan, dimethyl sulfide, etc.) are adsorbed (deodorized). The ratio of such a halitosis-preventing or removing component is, for example, 0.01 to 2% by weight, preferably 0.01 to 1% by weight, based on the whole tablet.
Examples of components that suppress the killing or growth of oral bacteria include nonionic fungicides, cationic fungicides, anionic fungicides, amphoteric fungicides, copper compounds, silver compounds, zinc compounds, and antibacterial agents. ..
Examples of the nonionic bactericide include fluorides such as sodium fluoride and sodium monofluorophosphate, phenols such as isopropylmethylphenol (3-methyl-4-isopropylmethylphenol), thymol, carvacrol, triclosan, and eugenol. Examples include sexual compound, thymol, limonene, and hinokithiol.
Examples of the cationic bactericide include cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, and berberine chloride.
Examples of the anionic bactericide include sodium lauryl sulfate, sodium polyoxyethylene lauryl ether sulfate, dodecylbenzenesulfonic acid, and sodium dodecylbenzenesulfonic acid.
Examples of the amphoteric bactericidal antibacterial agent include alkyldiaminoethylglycine hydrochloride and dodecyldiaminoethylglycine.
Examples of the copper compound include copper gluconate and copper sulfate.
Examples of the silver compound include silver zeolite.
Examples of the zinc compound include zinc chloride, zinc gluconate, zinc citrate, zinc acetate, zinc salicylate, zinc lactate, and zinc sulfate.
Examples of the antibacterial agent include fragrances containing ω-methylthioalkyl isothiocyanate.
Examples of the component that adsorbs (deodorizes) VSC include sodium copper chlorophyllin.
As a component for preventing or removing bad breath, a cationic bactericide such as cetylpyridinium chloride is preferably used.

The tablet of the present invention may further contain an enzyme having a tongue coating removing action, an enzyme having an effect of improving the tongue coating removing action, and a bacteriostatic agent. The ratio of such a halitosis-preventing or removing component is, for example, 0.1 to 10% by weight, preferably 0.5 to 3.5% by weight, based on the whole tablet.
Examples of the enzyme having a tongue moss removing action or the enzyme having an effect of improving the tongue moss removing action include protease, amylase, lipase, dextranase, trypsin, papain, bromelain, pectinase, pepsin, peptidase, phosphorlipase, muramidase, lysoteam and the like. Can be mentioned.
The bacteriostatic agent may be a substance that suppresses or blocks the growth of bacteria (streptococcus or staphylococcus), and examples thereof include polyphenols such as catechin.

The tablet in the present invention can be produced by a method characterized by mixing sorbitol granules and erythritol granules and tableting. For example, it can be produced by a method including the following steps.
First, sorbitol is granulated together with halitosis-preventing or removing components, other additives, etc., using a binder as needed. The granulation method is not particularly limited, and for example, known methods such as extrusion granulation, rolling granulation, stirring granulation, fluidized bed granulation, spray drying granulation, crush granulation, and melt granulation are used. For example, granulation handbook (edited by Japan Powder Industry Technology Association, Ohm Co., Ltd.), formulation design of orally administered preparations (edited by Professor Mitsuru Hashida, Graduate School of Pharmaceutical Sciences, Kyoto University, Yakuhin Jihosha), powder compression Molding Technology (Powder Engineering / Formulation and Particle Design Subcommittee, Nikkan Kogyo Shimbun), Formulation Machine Technology Handbook (2nd Edition, 20th Anniversary Publication Editorial Committee, Formulation Machine Technology Study Group) You can use the methods described in publications such as. If necessary, the obtained granulated product may be dried, sized, or the like by a method generally used for preparation.
Further, in the present invention, the granulation method is preferably fluidized bed granulation.

Next, erythritol granules are added to the granules together with a halitosis preventing or removing component and other additives and mixed. The mixing method is not particularly limited, but using the methods described in publications such as the above-mentioned granulation handbook, for example, various mixers generally used for preparations (for example, universal mixer, tumbler mixer, V type). It can be done using a mixer, etc.).
Further, in the present invention, the mixing method is preferably mixing using a container rotary mixer such as a tumbler mixer or a V-type mixer.

Then, using the method described in publications such as the granulation handbook exemplified above, the above mixture is used, for example, by using various tableting machines generally used for preparations (for example, a rotary type tableting machine). It can be tableted into tablets.

The weight of the tablet in the present invention is, for example, 100 mg to 1500 mg, preferably 200 mg to 600 mg per tablet.

The tablet in the present invention has an arbitrary shape, and examples thereof include a round shape, an oval shape, a caplet shape, a donut shape, and an oblong shape. Further, the tablet in the present invention has, for example, a thickness of 3 to 6 mm and a diameter of 8 to 14 mm.

The oral disintegration time of the tablet in the present invention is, for example, 10 seconds to 30 minutes, preferably 30 seconds to 15 minutes, and more preferably 3 to 7 minutes. As used herein, the term "oral disintegration time" refers to the time required for a tablet to completely disintegrate only with saliva in the oral cavity of healthy adult males and females.

The tablet in the present invention has an appropriate hardness or abrasion degree that is not damaged in the manufacturing process and the distribution process. The tablet hardness is, for example, 20 to 400 N, preferably 40 to 300 N, and more preferably 100 to 250 N. In the present specification, tablet hardness is measured by, for example, a tablet hardness tester. The degree of abrasion is, for example, about 1% or less, preferably about 0.5% or less. As used herein, the degree of abrasion is measured according to, for example, the abrasion test described in the Japanese Pharmacopoeia, the United States Pharmacopeia, or the European Pharmacopoeia.

The dose, frequency and duration of the tablet of the present invention are determined according to the condition of the user, the tongue coating score of the user, and the like.
The dose of the tablet in the present invention is, for example, 0.1 to 10 g at a time, preferably 0.2 to 3 g. The tablets of the present invention may be taken one tablet at a time, or a plurality of tablets (for example, 2 to 6 tablets) may be taken at a time. When taking a plurality of tablets, they may be taken at the same time or sequentially.
The frequency of taking tablets in the present invention is, for example, once, twice, three times, four times, five times, six times or more, preferably five or six times a day. The interval between doses of the tablets in the present invention is, for example, 30 minutes or more, preferably 2 hours or more. The timing of administration is not particularly limited, and is, for example, before meals, after meals, between meals, and preferably after meals. Before meals means from just before meals to about 30 minutes before eating, after meals means from immediately after meals to about 30 minutes after eating, and between meals means about 2 after eating meals. It means the time about 2 hours or more before the next meal after the time has passed.
The period for taking the tablet in the present invention is, for example, 2 weeks and 1 month, and the tablet may be taken permanently as needed.

The tablets of the present invention are preferably retained in the oral cavity without being swallowed when taken. If the residence time is too short, it is difficult to obtain the effect of removing tongue coating. Moreover, it is preferable that the tablet in the present invention is licked to the end without chewing.

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

[Example 1]
Sorbitol (SP, Bussan Food Science) and partially pregelatinized starch (PC-10, Asahi Kasei) are charged in a fluidized bed granulator (FD-3S, Paulec), and an aqueous solution of hydroxypropyl cellulose (HPC-L, Nippon Soda) is sprayed. After granulation and drying, the granules were sized with a 20-mesh sieve to obtain sized powder. The composition ratio of the sized powder was 87.6% sorbitol, 9.3% partially pregelatinized starch, and 3.0% HPC.
After dissolving l-menthol (Suzuki light load) in ethanol and adsorbing it on light anhydrous silicic acid (Syricia, Fuji Silysia Chemical), sized powder 82%, l-menthol 0.3%, light anhydrous silicic acid 0. With a composition of 7%, erythritol granules (Micro Foods Japan) 14.0%, magnesium stearate (vegetable, light, Taihei Kagaku Sangyo) 2.0%, crospovidone (corridon CL-F, BASF) 1.0% Mixing was carried out using a polyethylene bag to obtain a mixed powder.
The obtained mixed powder was tableted with a rotary tableting machine (AQU3-A, Kikusui Seisakusho) so as to be 500 mg per tablet to obtain tablets.

[Comparative Examples 1 to 6]
Various saccharide components (sorbitol, powdered maltose starch syrup, erythritol fine powder, xylitol, mannitol) and partially pregelatinized starch of the granulated portion are subjected to a fluidized layer granulator (FD-3S, It was charged in Paulec) and sprayed with an aqueous solution of hydroxypropyl cellulose (HPC-L, Nihon Soda) to granulate and dry, and then sized with a 20-mesh sieve to obtain sized powder. The composition ratio of the sized powder was 87.6% for sugar component, 9.3% for partially pregelatinized starch, and 3.0% for HPC.
After dissolving l-menthol (Suzuki light load) in ethanol and adsorbing it on light anhydrous silicic acid (Silicia, Fuji Silysia Chemical Ltd.), sized powder 82%, l-menthol 0.3%, light anhydrous silicic acid 0. 7%, various sugar components in the post-addition part (erythritol granules, mannitol, xylitol) 14.0%, magnesium stearate (vegetable, light, Taihei Chemical Industry) 2.0%, crospovidone (corridon CL-F, Mixing was carried out using a polyethylene bag having a composition of BASF) 1.0% to obtain a mixed powder.
The obtained mixed powder was tableted with a rotary tableting machine (AQU3-A, Kikusui Seisakusho) so as to have a concentration of 500 mg per tablet to obtain tablets.

[Test Example 1]
In Example 1 and Comparative Examples 1 to 6, the manufacturability of the granulation step and the tableting step was evaluated. The manufacturability in the granulation process was evaluated for the presence or absence of flow defects during granulation, and the manufacturability in the tableting process was evaluated for the presence or absence of capping and sticking during tableting.

Regarding the production of the granulation step, in Comparative Example 5 in which xylitol was blended in the granulation part, poor flow was observed due to the cohesiveness of xylitol during the granulation step, so that the granulation in this formulation was interrupted. Subsequent steps were not carried out. No flow failure was observed in the examples and other comparative examples. Regarding the manufacturability of the tableting process, in Comparative Examples other than Example and Comparative Example 5, tableting obstacles such as sticking of a pestle during tableting were not observed, and tableting was possible.

[Test Example 2]
The tablet hardness and the degree of tablet abrasion were evaluated for the tablets obtained in Example 1 and Comparative Examples 1 to 4 and 6 (tablets at a tableting pressure of about 24 KN). For the tablet hardness, the tablet hardness in the major axis direction was measured for 10 arbitrarily selected tablets using a hardness tester (TH-303, Toyama Sangyo), and the average value of the tablet hardness of a total of 10 tablets was calculated. For the tablet abrasion degree, the tablet abrasion degree is measured for 13 arbitrarily selected tablets using an abrasion degree tester (TFT-1200, Toyama Sangyo) in accordance with 17 Reference Information of the Japanese Pharmacopoeia / Tablet Abrasion Degree Test. did. In order to eliminate the weight increase due to the water content of the tablets, the tablets not subjected to the abrasion degree test were also left unattended during the test, and the abrasion degree of the tablets was calculated according to the following formula.
Tablet wear (%) = [(tablet mass before test-tablet mass after test) / (tablet mass before test)]-[(tablet mass before test-tablet mass left during the test period) / (test Previous tablet mass)]
In addition, the appearance of the tablet after abrasion was visually confirmed, and cracking and chipping of the tablet was evaluated.

The results are shown in Table 2 below. Regarding tablet hardness, while the tablet hardness of Comparative Examples 4 and 6 was low, the combination of granulated sorbitol / post-added erythritol granules in Example 1 and granulated sorbitol / post-added mannitol was compared. Example 1, Comparative Example 2 of the combination of the granulated portion sorbitol / the post-added portion xylitol showed a high tendency. As described above, the lot containing sorbitol in the granulated portion tended to have a high tablet hardness, but the lot containing powdered reduced malt starch syrup or mannitol in the post-addition portion tended to have a low tablet hardness. It was.
Regarding the degree of abrasion of the tablets, the tablets of Comparative Examples 4 and 6 which showed low tablet hardness had a high degree of abrasion, and many cracks and chips of the tablets having a degree of abrasion were observed.

[Test Example 3]
The tablets obtained in Example 1 and Comparative Examples 1 to 4 and 6 were subjected to sensory evaluation and measurement of oral disintegration time. When the tablet was licked by 5 monitors, (1) roughness (no roughness-strongly feels roughness), (2) sweetness (not sweetness-strongly sweetness), (3) refreshing feeling (3) 10 levels of menthol) (does not feel refreshing-feels refreshing strongly), (4) melts in the mouth (poor melts in the mouth-good melts in the mouth) and (5) ease of administration (poor ingestibility-good ingestion) Evaluated in. Regarding melting in the mouth, it was evaluated that there was no powderiness. As for the ingestibility, as a comprehensive evaluation, it was evaluated whether it conformed to the concept of a feeling of roughness on the tongue, which is a feature of this preparation, and a refreshing feeling. In addition, during the functionality test, the disintegration time in the oral cavity was measured.

The results are shown in Table 3 below. Regarding the sensory test, the scores of Example 1 and Comparative Example 4 were high for the graininess and refreshing sensation of the tablets at the time of administration, and the scores for the comprehensive evaluation of ingestibility were also high.
Regarding the oral disintegration time, the tablets disintegrated rapidly in Comparative Example 6, but the disintegration time was almost the same in the other Comparative Examples and Examples.

From the above results, according to the present invention, it is possible to provide a tablet having an excellent tablet hardness and tablet abrasion degree, which gives a feeling of roughness on the tongue, an excellent feeling of ingestion, and no feeling of powderiness. It is possible to reduce cracking and chipping of tablets in the tablet manufacturing process and filling process.

[Manufacturing Example 1]
After dissolving l-menthol (Suzuki light load) in ethanol and adsorbing it on light silicic acid anhydride (Syricia, Fuji Silysia Chemical), cetylpyridinium chloride (Wako Pure Chemical Industries) 0.1%, sorbitol granules (NEOSORB XTAB 290S) , Rocket Japan) 70%, l-menthol 0.3%, light anhydrous silicic acid 0.7%, erythritol granules (Micro Foods Japan) 24.0%, partially pregelatinized starch (PC-10, Asahi Kasei) 2.4 Using a mixer (tumbler mixer, Showa Kagaku Kikai) with a composition of%, magnesium stearate (vegetable, light, Taihei Kagaku Sangyo) 1.5%, crospovidone (corridon CL-F, BASF) 1.0% And mixed to obtain a mixed powder.
The obtained mixed powder was tableted with a rotary tableting machine (AQU3-A, Kikusui Seisakusho) so as to have a concentration of 500 mg per tablet to obtain tablets.

[Manufacturing Example 2]
Cetylpyridinium chloride (Wako Pure Chemical Industries, Ltd.), sorbitol (SP, Bussan Food Science), partially pregelatinized starch (PC-10, Asahi Kasei) were charged into a fluidized layer granulator (FD-3S, Paulec), and sodium copper chlorophyllin (sodium copper chlorophyllin) ( By spraying an aqueous solution of hydroxypropyl cellulose (HPC-L, Nihon Soda) in which Tama Biochemistry is dissolved, granulation and drying are performed, and then granulation is performed using a granulator (Power Mill P-3S, Showa Kagaku Kikai). And obtained the sized powder. The composition ratio of the sized powder was cetylpyridinium chloride 0.2%, sorbitol 87.2%, partially pregelatinized starch 9.3%, hydroxypropyl cellulose 3.0%, and copper chlorophyrin sodium 0.1%.
After dissolving l-menthol (Suzuki light load) in ethanol and adsorbing it on light anhydrous silicic acid (Syricia 320, Fuji Silysia Chemical), 82.0% of sized powder, ω-methylthioalkylisothiocianate-containing fragrance (Wasadent) -Clear menthol, Ogawa fragrance) 0.1%, l-menthol 0.3%, Silysia 0.7%, erythritol granules (Micro Foods Japan) 14.0%, crospovidone (Corridon CL-F, BASF) 1. Mixing was performed using a mixer (tumbler mixer, Showa Kagaku Kikai) with a composition of 0% and magnesium stearate (vegetable, light, Taihei Kagaku Kogyo) 2.0% to obtain a mixed powder for tableting. The obtained mixed powder for tableting was tableted with a rotary tableting machine (AQU3, Kikusui Seisakusho) so that the uncoated mass was 500 mg, and tablets were obtained.

[Manufacturing Example 3]
Sorbitol (SP, Bussan Food Science) and partially pregelatinized starch (PC-10, Asahi Kasei) are charged in a fluidized bed granulator (FD-3S, Paulec), and an aqueous solution of hydroxypropyl cellulose (HPC-L, Nippon Soda) is sprayed. After granulation and drying, granulation was performed with a granulator (Power Mill P-3S, Showa Kagaku Kikai) to obtain granulated powder A. The composition ratio of the sized powder A was cetylpyridinium chloride 0.3%, sorbitol 91.7%, partially pregelatinized starch 5%, and hydroxypropyl cellulose 3%.
Furthermore, papain (Mitsubishi Chemical Foods), erythritol (100M, Bussan Food Science), and lactose (Megre Japan) are charged in a fluidized bed granulator and sprayed with HPC-L solution to granulate, dry, and then prepare. The granules were sized with a granulator (power mill) to obtain a sized powder B. The composition ratio of the sized powder B was 0.3% papain, 85% erythritol, 11.6% lactose, and 3.1% hydroxypropyl cellulose.
After dissolving l-menthol (Suzuki light load) in ethanol and adsorbing it on light anhydrous silicic acid (Syricia 320, Fuji Silysia Chemical Ltd.), sizing powder A67.3%, sizing powder B28.3%, crystalline cellulose 1 .3%, l-menthol 0.3%, anhydrous calcium phosphate (Fujicarin, Fuji Chemical) 0.7%, crospovidone (corridon CL-F, BASF) 1.0%, magnesium stearate (vegetable, light, Taihei Kagaku Kogyo) Mixing using a mixer (tumbler mixer, Showa Kagaku Kikai) with a composition of 1.0% to obtain a mixed powder for tableting. The obtained mixed powder for tableting was tableted with a rotary tableting machine (AQU3, Kikusui Seisakusho) so as to have an uncoated mass of 495 mg to obtain tablets.

According to the present invention, by imparting an appropriate degree of roughness to a tablet, it is expected that tongue coating, which is the main cause of bad breath, can be removed, and a tablet having an excellent feeling of administration without feeling powdery at the time of administration can be provided. Can be done. Further, according to the present invention, it is intended to provide a tablet having a disintegration time suitable for the purpose of removing tongue coating and having excellent tablet hardness and tablet abrasion degree to reduce cracking and chipping of tablets in a manufacturing process and a filling process. Can be done.

Claims (6)

A method for producing tablets containing sorbitol and erythritol.
A method for producing a tablet, which comprises mixing sorbitol granules and erythritol granules and tableting them. The production method according to claim 1, wherein 60% by weight to 90% by weight of sorbitol and 10% to 40% by weight of erythritol are blended with respect to the entire tablet. The production method according to claim 1 or 2, wherein modified starch is added. The production method according to any one of claims 1 to 3, wherein a halitosis-preventing or removing component is added. The production method according to any one of claims 1 to 4, wherein the disintegration time of the tablet in the oral cavity is 30 seconds to 15 minutes. The production method according to any one of claims 1 to 5, wherein the tablet is for preventing or removing bad breath.