Tablet and method for producing tablet

Abstract

To provide a tablet that is easy to swallow and also has reduced production cost, and a method of producing the same.SOLUTION: A tablet has a naked tablet containing a gelator, and at least one selected from sugar alcohol, monosaccharide, disaccharide, oligosaccharide, cellulose, cellulose derivative, starch, starch derivative and starch decomposition product. Preferably, the gelator is at least one selected from xanthan gum, locust bean gum, guar gum, mannan, glucomannan, hyaluronan, agar, alginic acid, tamarind gum, psyllium seed gum, tara gum, carrageenan, acacia gum, gum arabic, ghatti gum, tragacanth gum, karaya gum, cassia gum, rhamsan gum, welan gum, macrophomopsis gum, curdlan, pullulan, gellan gum, pectin, and soybean polysaccharide, gelatin, collagen, polyglutamic acid, polylactic acid, polyglutamic acid and the like.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a tablet and a method for producing the same. [Background technology]

[0002] With the recent rise in health consciousness among consumers and the introduction of the Functional Food Labeling System as a new food labeling system, the market size of health foods and supplements in Japan is expected to continue to expand. Tablets are often used as oral formulations among supplements, but taking large tablets or multiple tablets at the same time can be difficult for people who have difficulty swallowing tablets, especially children and the elderly who have poor swallowing function. To make tablets easier to swallow, it is necessary to improve the tablet's slipperiness, the difficulty of it getting stuck in the throat, etc. Taking this into consideration, several technologies that have been developed to coat solid preparations such as tablets have been reported (Patent Documents 1 to 3). However, even if coating makes the tablet surface slippery and improves swallowing to a certain extent, the resistance when passing through the complexly shaped pharynx remains large, and the effect of improving swallowing is not sufficient. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 11-60472 [Patent Document 2] Special Publication No. 2011-502132 [Patent Document 3] Special Publication No. 2014-534977 Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention aims to provide a tablet that can be easily taken with little resistance even by people who have difficulty swallowing tablets. Furthermore, while conventional coated tablets tend to increase in volume due to the coating layer, and the coating is applied to the tablet surface after tableting, which requires time and effort and manufacturing costs, the present invention aims to provide a tablet that prevents tablets from becoming large, and that is easy to swallow and also reduces manufacturing costs. [Means for solving the problem]

[0005] The present invention relates to a method for producing a gelling agent. The present invention provides a tablet having a core containing one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates.

[0006] The present invention also provides a method for producing the above-mentioned tablets, which comprises compressing a raw material powder containing a gelling agent and one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates into tablets having a plain tablet. [Effects of the Invention]

[0007] The tablet having a bare tablet of the present invention is characterized in that when the bare tablet portion comes into contact with saliva or ingested moisture (hereinafter referred to as a liquid medium such as water), it absorbs the liquid medium such as water and becomes elastic, causing a slimy feeling on the surface of the tablet having a bare tablet, making it easy to swallow. Here, liquid medium such as water means water, tea, soft drinks, milk, other aqueous liquids commonly consumed, saliva, or a mixture thereof. Furthermore, since the entire surface of the tablet having a bare tablet of the present invention is not covered with a coating layer, production costs can be reduced and the tablet size can be prevented from increasing. Furthermore, the tablet having a bare tablet of the present invention also has excellent ease of disintegration after ingestion. Furthermore, the method for producing the core tablet of the present invention is an industrially advantageous method for producing the core tablet of the present invention. [Brief explanation of the drawings]

[0008] [Figure 1] Figure 1 is a conceptual diagram of the method for measuring maximum stress. [Figure 2] Figure 2 shows the electromyogram when only water was taken. [Figure 3] FIG. 3 shows an electromyogram when the tablet produced in Example 1 was taken. [Figure 4] FIG. 4 shows an electromyogram when the tablet produced in Example 2 was taken. DETAILED DESCRIPTION OF THE INVENTION

[0009] The present invention will be described below based on preferred embodiments thereof.

[0010] The tablet of the present invention has a bare tablet containing a gelling agent and one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates. Generally, a bare tablet (also called a plain tablet) refers to a tablet on whose surface no coating layer is formed. In this specification, "a tablet having a bare tablet" means a tablet having a portion on its surface on which no coating layer is formed, and said portion is in a bare tablet state (hereinafter, the portion on the tablet surface on which no coating layer is formed is referred to as the bare tablet portion). Furthermore, in this specification, "bare tablet" means a tablet on whose surface no coating layer is substantially formed (a tablet in which the proportion of the area covered by the coating layer to the surface area of ​​the tablet is less than 5%). In this specification, "bare tablet" is a concept that is included in "a tablet having a bare tablet".

[0011] The tablet having the naked tablet of this embodiment exhibits a slimy property (also referred to as slipperiness) when a liquid medium such as water comes into contact with the naked tablet portion. The tablet having the naked tablet of this embodiment preferably has a gelling agent on the outermost surface of the naked tablet portion. The outermost surface refers to the portion located on the surface side of the naked tablet portion, and refers to a range of 0 mm to 1 mm from the surface of the naked tablet portion toward the center. The tablet of this embodiment has a gelling agent on the outermost surface of the naked tablet portion, particularly the outermost surface of the naked tablet portion, so that the surface of the naked tablet portion becomes slimy when it comes into contact with a liquid medium such as water. As a result, the tablet having the naked tablet of this embodiment is easy to swallow even without providing a coating layer. It is particularly preferable that the tablet having the naked tablet has a gelling agent on the entire outermost surface of the naked tablet portion. In this specification, if it is confirmed that a gelling agent is present at two or more different locations on the outermost surface of the naked tablet portion, it can be said that the gelling agent is present on the entire outermost surface of the naked tablet portion. The presence of a gelling agent on the surface can be confirmed by scraping off about 30 mg of any part of the outermost surface with a scalpel or the like and adding an appropriate amount of liquid medium such as water to cause gelation. As will be described later, a tablet having a plain tablet in which the gelling agent is present on the entire outermost surface of the plain tablet portion can be easily obtained as a compressed product of a mixed powder containing a gelling agent and a specific excipient.

[0012] In the case of the tablet having a naked tablet of the present invention, the presence of the naked tablet portion allows the effect of the gelling agent to be exerted, so it is preferable that the naked tablet portion be present on the outermost surface of the tablet. Specifically, the proportion of the surface area occupied by the naked tablet portion on the outermost surface of the tablet is preferably 70% or more, more preferably 90% or more, and particularly preferably 95% or more. Furthermore, when the tablet having a naked tablet of the present invention has a coating layer, the proportion of the surface area of ​​the tablet covered by the coating layer is preferably less than 30%, particularly preferably less than 10%, and most preferably there is substantially no coating layer (meaning that the proportion of the area covered by the coating layer to the surface area of ​​the tablet is less than 5%). Furthermore, when the tablet having a naked tablet of the present invention has a coating layer, the thickness of the coating layer from the surface of the naked tablet portion toward the center is preferably 3 mm or less, more preferably 2 mm or less, and particularly preferably 1 mm or less. By making the thickness of the coating layer 1 mm or less, the effect of the gelling agent can be easily exerted, production costs can be reduced, and the tablet can be prevented from becoming large. When the coating layer covers only a portion of the tablet, the coating layer may be present continuously but unevenly distributed in a part of the tablet, or may be dispersed in an island form, etc. For example, if a powdery substance other than a gelling agent (e.g., sugars or other seasonings) is sprinkled on the surface of the plain tablet, so that the coating layer is present on only a part of the tablet surface, this is acceptable because the gelling agent present in the plain tablet portion exerts its effect.

[0013] The tablet having a naked tablet may have a structure in which the surface portion and the portion closer to the center are distinguished, or may not have such a structure. For example, the tablet having a naked tablet may have a multi-layer structure like a dry-coated tablet. Among them, when the tablet having a naked tablet does not have a multi-layer structure but has a single-layer structure, it is preferable in terms of ease of production, etc.

[0014] 1. Gelling agent Tablets having a naked tablet contain a gelling agent. In the present invention, it is preferable that a gelling agent be present in the outermost surface portion of a tablet having a naked tablet, but a gelling agent may be present in a portion other than the outermost surface portion. For example, a tablet having a naked tablet may contain a gelling agent in both the outermost surface portion and the portion closer to the center (also referred to as the center portion). An example of such a tablet having a naked tablet is a tablet having a single-layer structure. In a tablet having a naked tablet, the composition of the outermost surface portion and the composition of the center portion may be the same or different, but it is preferable that they are the same from the viewpoint of ease of manufacturing a tablet having a naked tablet. The presence of a gelling agent in the center of a tablet having a naked tablet can be confirmed, for example, by cutting a tablet having a naked tablet in half with a cutter or the like, scraping off about 30 mg of the tablet at any position more than 1 mm from the surface toward the center with a scalpel or the like, and adding an appropriate amount of liquid medium such as water to gel it. Note that the components listed as disintegrants below are not included in the gelling agent in this application.

[0015] The gelling agent used is a powder (particulate) substance that exhibits a slimy texture when containing a liquid medium such as water. Examples of gelling agents include natural polysaccharides such as xanthan gum, locust bean gum, guar gum, mannan, glucomannan, hyaluronic acid, agar, alginic acid, tamarind gum, psyllium seed gum, tara gum, carrageenan, acacia gum, gum arabic, gum ghatti, tragacanth gum, karaya gum, cassia gum, rhamsan gum, welan gum, macrophomopsis gum, curdlan, pullulan, gellan gum (deacylated gellan gum, native gellan gum), pectin, and soybean polysaccharides; protein hydrolysates such as collagen; polyamino acids such as polyglutamic acid; biopolymers such as polylactic acid and polyglutamic acid, and salts and derivatives thereof. Natural polysaccharides are particularly preferred. Examples of the derivatives include hyaluronic acid derivatives, alginic acid derivatives, and polyglutamic acid derivatives. Examples of the salts include alginates, hyaluronates, and polyglutamates. Examples of hyaluronic acid derivatives include hyaluronic acid esters and acetylated hyaluronic acid. Examples of alginic acid derivatives include alginic acid esters. Examples of polyglutamic acid derivatives include polyglutamic acid esters. Examples of alginates include sodium alginate, potassium alginate, ammonium alginate, and calcium alginate. Examples of hyaluronates include sodium hyaluronate and potassium hyaluronate. Examples of polyglutamates include sodium polyglutamate and potassium polyglutamate. One type of gelling agent may be used alone, or two or more types may be used in combination.

[0016] In this embodiment, the gelling agent preferably contains one or more selected from locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, gum arabic, gum ghatti, tragacanth gum, karaya gum, cassia gum, rhamsan gum, welan gum, macrophomopsis gum, curdlan, pullulan, gellan gum, polyamino acids, polylactic acid, and salts and derivatives thereof (hereinafter also referred to as specific gelling agents), as these are easily broken down in the body after ingestion, and in particular, it is preferable to contain locust bean gum, as this not only provides excellent ease of disintegration after ingestion, but also provides a high level of both disintegrability and sliminess.

[0017] Combining two or more gelling agents is also preferred from the viewpoint of achieving both disintegration and sliminess and from the viewpoint of manufacturability, and combining a specific gelling agent with a gelling agent other than the specific gelling agent is even more preferred. Specifically, it is preferred to combine locust bean gum, which is a specific gelling agent, with xanthan gum, guar gum, alginic acid, carrageenan, or the like, which is a gelling agent other than the specific gelling agent. For example, combining xanthan gum or guar gum with locust bean gum can effectively improve ease of swallowing due to the slimy texture. Furthermore, combining guar gum with locust bean gum can provide a tablet with excellent disintegration properties in the body after ingestion.

[0018] In a tablet having a core tablet, the proportion of gelling agent is preferably 0.01% by mass or more in order to sufficiently generate a slimy feeling when contacted with a liquid medium such as water. Furthermore, the proportion of gelling agent in a tablet having a core tablet is preferably 70% by mass or less from the viewpoint of ease of dissolution of the active ingredient. From these points of view, the proportion of gelling agent in a tablet having a core tablet is more preferably 0.1% by mass or more and 60% by mass or less, even more preferably 1% by mass or more and 50% by mass or less, even more preferably 3% by mass or more and 30% by mass or less, and most preferably 5% by mass or more and 20% by mass or less. When the tablet having a core tablet of this embodiment contains at least one selected from the specific gelling agents in the tablet having a core tablet, the preferred range of the total mass of the specific gelling agent in the tablet having a core tablet is the same as the preferred range of the gelling agent. Here, the total mass of at least one type selected from the specific gelling agents refers to the mass of that one type when the tablet having a plain tablet contains only one type selected from the specific gelling agents, and refers to the total mass of those types when the tablet having a plain tablet contains two or more types of these.

[0019] When the tablet having a plain tablet of the present invention contains a specific gelling agent and other gelling agents, the ratio of the specific gelling agent to other gelling agents in the tablet having a plain tablet is, from the viewpoint of achieving both sliminess and disintegrability, preferably 10 parts by mass or more and 1,000 parts by mass or less of the former to 100 parts by mass of the latter, more preferably 15 parts by mass or more and 900 parts by mass or less, and particularly preferably 20 parts by mass or more and 800 parts by mass or less.

[0020] For example, when a tablet having a plain tablet of the present invention contains xanthan gum and locust bean gum, the ratio of the former to the latter in the tablet having a plain tablet is, in order to increase the slipperiness and the content of the active ingredient, more preferably 10 parts by mass or more and 1,000 parts by mass or less of locust bean gum per 100 parts by mass of xanthan gum, even more preferably 15 parts by mass or more and 900 parts by mass or less, and particularly preferably 20 parts by mass or more and 800 parts by mass or less.

[0021] Furthermore, when the tablet having a plain tablet of the present invention contains guar gum and locust bean gum, the ratio of the former to the latter in the tablet having a plain tablet is more preferably 10 parts by mass or more and 1000 parts by mass or less of locust bean gum per 100 parts by mass of guar gum, in order to increase the sliminess and the content of active ingredients, even more preferably 15 parts by mass or more and 900 parts by mass or less, and particularly preferably 20 parts by mass or more and 800 parts by mass or less.

[0022] 2. Specific excipients The tablets having a plain tablet contain one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates (hereinafter, these are also referred to as specific excipients). By combining a gelling agent with these specific excipients, tablets with excellent slipperiness and short disintegration time can be obtained.

[0023] As described above, the tablet having a plain tablet may contain one or more selected from monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates. However, in order to achieve both disintegration and sliminess, it is preferable to contain a combination of two or more components belonging to different categories. Specific examples include a combination of disaccharides and cellulose, a combination of disaccharides and reduced maltose, and a combination of disaccharides and starch. It is even more preferable to contain a combination of three or more components belonging to different categories. Specific examples include a combination of disaccharides, starch, and cellulose, and a combination of disaccharides, reduced maltose, and cellulose.

[0024] Sugar alcohols include monosaccharide alcohols, disaccharide alcohols, and trisaccharide or higher saccharide alcohols. Examples of monosaccharide alcohols include tetritols such as erythritol, D-threitol, and L-threitol; pentitols such as D-arabinitol and xylitol; hexitols such as D-iditol, galactitol (dulcitol), and D-glucitol (sorbitol); cyclitols such as inositol; mannitol, volemitol, ribitol, perseitol, and D-erythro-D-galacto-octitol. Examples of disaccharide alcohols include reduced maltose (maltitol), lactitol, and reduced palatinose (isomalt). Examples of trisaccharide or higher saccharide alcohols include maltotriitol, isomaltotriitol, and panitol. As the sugar alcohol, from the viewpoint of manufacturability, such as obtaining the hardness of the compressed tablets, it is preferable to use at least one type selected from disaccharide alcohols, and in particular, it is preferable to use at least one type selected from reduced maltose and reduced palatinose.

[0025] Examples of monosaccharides include glucose, galactose, fructose, and mannose. Among these, glucose is preferred in terms of availability and achieving both disintegration and sliminess.

[0026] Examples of disaccharides include sucrose, maltose, lactose (milk sugar), trehalose, turanose, and cellobiose. Among these, one or more selected from trehalose, sucrose, and maltose are preferred from the viewpoint of achieving both disintegrability and sliminess, and sucrose and maltose are particularly preferred. Although the effects of the present invention can be obtained even when lactose is contained, from the viewpoint of achieving both disintegrability and sliminess, it is more preferred that the disaccharide be a disaccharide other than lactose.

[0027] Examples of oligosaccharides include those containing from three to twenty saccharides, preferably from three to ten saccharides, and more preferably from three to six saccharides. Specific examples include raffinose, maltotriose, melezitose, gentianose, acarbose, stachyose, galactooligosaccharides, fructooligosaccharides, mannanoligosaccharides, isomaltooligosaccharides (isomaltotriose, panose), xylooligosaccharides, soybean oligosaccharides, nigerooligosaccharides, and lactoferrin oligosaccharides. Isomaltooligosaccharides or fructooligosaccharides are particularly preferred in terms of availability and achieving both disintegratability and sliminess.

[0028] It is preferable that the tablet having a plain tablet contains any one of monosaccharides, disaccharides, and oligosaccharides from the viewpoint of taste masking and promoting saliva secretion. It is particularly preferable that the surface of the tablet having a plain tablet contains such a saccharide.

[0029] Examples of cellulose include powdered cellulose and crystalline cellulose. Crystalline cellulose is obtained by partially depolymerizing α-cellulose obtained as pulp from fibrous plants with acid and purifying it. For example, the crystalline cellulose described in the 15th revised Japanese Pharmacopoeia Commentary (published by Hirokawa Shoten) can be mentioned. Crystalline cellulose can be classified into crystalline cellulose powder and crystalline cellulose complex, and both of these can be used for the tablet having the plain tablet of the present invention.

[0030] Examples of cellulose derivatives include carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, and methyl cellulose. Carboxymethyl cellulose with a degree of etherification of 0.2 mol / C6 to 1.0 mol / C6 is preferred from the viewpoints of availability and achieving both sliminess and disintegration time, with carboxymethyl cellulose with a degree of etherification of 0.5 mol / C6 to 0.8 mol / C6 being more preferred. Although the effects of the present invention can be obtained even when croscarmellose sodium or low-substituted hydroxypropyl cellulose, which are internally crosslinked with carboxymethyl cellulose sodium, is contained, from the viewpoint of achieving both disintegration and sliminess, it is more preferred that the cellulose derivative be a cellulose derivative other than croscarmellose sodium and low-substituted hydroxypropyl cellulose.

[0031] Examples of starch include natural starch. Starch can be derived from corn, potato, arrowroot, tapioca, sweet potato, rice, wheat, barley, yam, taro, etc. When starch is added, it is particularly preferable to add it in combination with a sugar alcohol in order to achieve both disintegration property and slimy property.

[0032] Examples of starch derivatives include modified starch, oxidized starch, enzyme-treated starch, pregelatinized starch, starch phosphate, distarch phosphate, starch acetate, starch octenyl succinate, glycerol distarch, carboxymethyl starch, hydroxypropyl starch, crosslinked starch, soluble starch, grafted starch, and sodium carboxymethyl starch, with pregelatinized starch being preferred in terms of achieving both sliminess and disintegration time.When incorporating a starch derivative, it is particularly preferred to incorporate it in combination with a sugar alcohol in order to achieve both disintegration and sliminess.Note that although the effects of the present invention can be obtained even when sodium carboxymethyl starch is included, from the viewpoint of achieving both disintegration and sliminess, it is more preferred that the starch derivative be a starch derivative other than sodium carboxymethyl starch.

[0033] Examples of starch decomposition products include dextrin, and those with a DE of 8 to 9.5 are preferred.

[0034] The content of the specific excipient in the tablet having a plain tablet is preferably 10 parts by mass or more relative to 100 parts by mass of the gelling agent in the tablet having a plain tablet, from the viewpoint of further enhancing the effect of using the gelling agent and the specific excipient in combination, and the amount of the specific excipient is preferably 3000 parts by mass or less relative to 100 parts by mass of the gelling agent in the tablet having a plain tablet, from the viewpoint of increasing the content of the active ingredient. From these points of view, the amount of the specific excipient in the tablet having a plain tablet is preferably 10 parts by mass or more and 3000 parts by mass or less, more preferably 20 parts by mass or more and 2500 parts by mass or less, and particularly preferably 30 parts by mass or more and 2000 parts by mass or less relative to 100 parts by mass of the gelling agent in the tablet having a plain tablet.

[0035] Furthermore, the amount of the specific excipient is preferably 1 part by mass or more and 90 parts by mass or less, more preferably 2 parts by mass or more and 80 parts by mass or less, and most preferably 3 parts by mass or more and 70 parts by mass or less, relative to 100 parts by mass of the tablet having the plain tablet. In particular, from the viewpoint of disintegration, the specific excipient preferably accounts for 40% by mass or more of the tablet having the plain tablet, more preferably 50% by mass or more, even more preferably 60% by mass or more, and may even be 70% by mass or more. Furthermore, the upper limit of the amount of the specific excipient is preferably 95% by mass or less of the tablet having the plain tablet in terms of containing a gelling agent, and more preferably 90% by mass or less.

[0036] The tablets having a plain tablet in the present invention preferably contain one or more selected from among specific excipients such as monosaccharides, disaccharides, oligosaccharides, starch derivatives (particularly pregelatinized starch) and starch hydrolysates, as these have high sliminess, and it is even more preferable for them to contain monosaccharides, disaccharides, oligosaccharides or starch hydrolysates.

[0037] In addition, it is preferable for tablets having a plain tablet to contain a monosaccharide, disaccharide, oligosaccharide, sugar alcohol, crystalline cellulose or a cellulose derivative (particularly carboxymethylcellulose) as a specific excipient, from the viewpoint of excellent disintegrability in addition to sliminess, and it is even more preferable for the tablet to contain a monosaccharide, disaccharide, oligosaccharide, sugar alcohol or carboxymethylcellulose. In addition, the inclusion of sugar alcohols and disaccharides is also preferable in that it increases the binding properties of the raw material powder of the tablet, making it easier to formulate the tablet by achieving the desired hardness, and also in that it has the effect of masking the unpleasant taste of the active ingredient.

[0038] It is most preferable that monosaccharides, disaccharides, oligosaccharides, sugar alcohols, crystalline cellulose, and carboxymethyl cellulose are contained as the main components in the specific excipient, specifically as components that account for 50% by mass or more of the specific excipient.

[0039] In addition, it is preferable that the tablet having a plain tablet contains a combination of a disaccharide and one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch, and starch hydrolysates as a specific excipient from the viewpoint of improving disintegrability and sliminess, and a combination of a disaccharide and an oligosaccharide or a cellulose derivative is particularly preferred. When the tablet having a plain tablet contains a combination of a disaccharide and another specific excipient as a specific excipient, from the viewpoint of achieving both sliminess and disintegrability, the other specific excipient is more preferably 1 part by mass or more and 1000 parts by mass or less, more preferably 5 parts by mass or more and 300 parts by mass or less, and particularly preferably 5 parts by mass or more and 100 parts by mass or less, per 100 parts by mass of the disaccharide.

[0040] Furthermore, from the viewpoint of improving disintegrability and sliminess, it is preferable that the tablet having a plain tablet contains a combination of a sugar alcohol and starch or pregelatinized starch as a specific excipient. When the tablet having a plain tablet contains a combination of a sugar alcohol and starch or pregelatinized starch as a specific excipient, from the viewpoint of achieving both sliminess and disintegrability, the amount of starch or pregelatinized starch is more preferably 10 parts by mass or more and 1000 parts by mass or less, even more preferably 30 parts by mass or more and 700 parts by mass or less, and particularly preferably 50 parts by mass or more and 500 parts by mass or less, per 100 parts by mass of the sugar alcohol.

[0041] In this embodiment, it is also preferable to contain starch, a starch derivative or a starch hydrolysate and combine this with xanthan gum, locust bean gum and guar gum, as well as salts and derivatives thereof, particularly locust bean gum, as this makes it easier to obtain a tablet having a good balance between hardness and degree of gelling, which is easy to swallow and has a plain tablet. As will be described later, it is also preferable to combine a sugar alcohol with at least one selected from xanthan gum, locust bean gum, guar gum, and salts and derivatives thereof, under the condition that the sugar alcohol and particles containing a gelling agent whose surface are coated with a gelling agent are not contained, in that this makes it easier to obtain a tablet that is excellent in hardness, ease of swallowing, and smoothness.Furthermore, as will be described later, it is also preferable that the tablet has a plain tablet containing reduced maltose and a gelling agent composed of at least one selected from starch and xanthan gum, locust bean gum, guar gum, and salts and derivatives thereof, under the condition that the coating layer of a gelling agent is not contained.

[0042] A tablet having a plain tablet preferably contains a specific excipient in the outermost surface portion of the plain tablet portion, and more preferably also in the center portion.

[0043] 3. Other ingredients The tablet having a plain tablet preferably contains silicon dioxide or the like as a flowability improver. Examples of silicon dioxide include fine silicon dioxide and light anhydrous silicic acid. When silicon dioxide is contained, the amount of silicon dioxide is preferably 0.01 parts by mass or more and 2 parts by mass or less, more preferably 0.1 parts by mass or more and 1.8 parts by mass or less, even more preferably 0.5 parts by mass or more and 1.7 parts by mass or less, and most preferably 1 part by mass or more and 1.5 parts by mass or less, relative to 100 parts by mass of the tablet having a plain tablet.

[0044] It is preferable that the tablets having a plain tablet contain a lubricant in terms of improving productivity (preventing punch sticking during tableting). Examples of lubricants include magnesium stearate and calcium stearate. When a lubricant is contained, the proportion thereof in the plain tablet of the present invention is preferably 0.1% by mass or more and 20% by mass or less, and more preferably 0.5% by mass or more and 10% by mass or less.

[0045] The tablet having a plain tablet according to this embodiment may contain an active ingredient. The active ingredient here may be a drug, a functional ingredient other than a drug, or a processed product derived from a plant, animal, or microorganism. The tablet having a plain tablet may contain the active ingredient, specific excipients, silicon dioxide, disintegrants, lubricants, sugars, as well as binders, seasonings other than sugars, emulsifiers, flavorings, etc. Furthermore, the tablet used in this embodiment is for oral administration, that is, for internal use, and is a tablet to be swallowed. Needless to say, the tablet of this embodiment may be used as a supplement, health food, nutrient-functional food, functional food, food for specified health uses, and pharmaceuticals.

[0046] The tablet having a core tablet of this embodiment contains a seasoning and / or flavoring other than sugars on the outermost surface of the core tablet portion, which promotes saliva secretion when the tablet having a core tablet is placed in the oral cavity, thereby increasing the supply of liquid media such as water to the tablet. Examples of the seasoning include sweeteners and acidulants. Examples of sweeteners that can be used include sucrose derivatives of sucralose, peptide sweeteners such as aspartame, alitame, neotame, and glycyrrhizin, stevia, and licorice. Examples of acidulants that can be used include organic acids, such as citric acid, malic acid, and tartaric acid. Examples of flavorings that can be used include citrus flavors such as grapefruit flavor, lemon flavor, and orange flavor, as well as fruit flavors.

[0047] The tablet having a core tablet according to this embodiment may contain a disintegrant. Examples of disintegrants include sodium bicarbonate (sodium bicarbonate), magnesium carbonate, carmellose calcium, sodium starch glycolate, etc., which can be used as food additives, as well as crospovidone, sodium carboxymethyl starch, croscarmellose sodium, and low-substituted hydroxypropyl cellulose. Although the effects of the present invention are exhibited even when a disintegrant is contained, from the viewpoint of excellent slipperiness, the content of the disintegrant is preferably low. Specifically, the amount of disintegrant is preferably 9.9 parts by weight or less, more preferably 9 parts by weight or less, even more preferably 6 parts by weight or less, even more preferably 3 parts by weight or less, particularly preferably 1 part by weight or less, and most preferably not contained, relative to 100 parts by weight of the tablet having a core tablet.

[0048] Among the disintegrants, from the viewpoint of excellent slipperiness, the content of one or more disintegrants selected from crospovidone, carboxymethyl starch sodium, croscarmellose sodium, or low-substituted hydroxypropyl cellulose (hereinafter also referred to as "specific disintegrants") is preferably low. Specifically, the amount of disintegrant is preferably 9.9 parts by weight or less, more preferably 9 parts by weight or less, even more preferably 6 parts by weight or less, even more preferably 3 parts by weight or less, extremely preferably 1 part by weight or less, and most preferably none at all, per 100 parts by weight of the plain tablet. Low-substituted hydroxypropyl cellulose is produced by reacting propylene oxide with alkali cellulose at high temperature, and refers to a product dried at 105°C for 1 hour that contains 5.0 to 16.0% hydroxypropyl groups.

[0049] The tablet having a plain tablet according to this embodiment may contain particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent. Although the effects of the present invention are exhibited even when particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent are included, from the viewpoint of excellent disintegration properties, it is preferable that the content of particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent is low. The amount of particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent per 100 parts by weight of the tablet having a plain tablet is preferably 10 parts by weight or less, more preferably 5 parts by weight or less, even more preferably 3 parts by weight or less, even more preferably 1 part by weight or less, and most preferably non-containing. Particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent are formed by spraying a gelling agent onto particles containing a sugar alcohol. In the present invention, the tablet having a plain tablet does not contain particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent, and the gelling agent and a specific excipient are uniformly mixed, which makes it easier to shorten the disintegration time.

[0050] The absence of particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent can be confirmed, for example, by examining the distribution of the gelling agent in a tablet having a plain tablet by cross-sectional imaging such as TOF-SIMS. In this case, if no layer in which the gelling agent is locally concentrated is observed and the gelling agent is uniformly dispersed in the plain tablet, it can be said that the tablet having a plain tablet of the present invention does not contain particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent.

[0051] 4.Physical properties etc. In consideration of ease of swallowing, for example, in the case of a disc-shaped tablet, the weight of one tablet is preferably 100 mg to 500 mg, more preferably 120 mg to 450 mg, and most preferably 150 mg to 400 mg. The diameter is preferably 5 mm to 12 mm, more preferably 5.5 mm to 11 mm, and most preferably 6 mm to 10 mm. The thickness is preferably 2 mm to 10 mm, more preferably 2.5 mm to 9 mm, and most preferably 3 mm to 8 mm. The hardness is preferably 3 kgf to 20 kgf, more preferably 4 kgf to 18 kgf, and most preferably 5 kgf to 16 kgf. The diameter, thickness, and hardness can be measured by the methods described below.

[0052] Furthermore, the maximum stress (maximum stress) generated when the tablet having a core tablet of the present invention moves through a silicone tube can be measured by the method described below. Specifically, the tablet is placed on a plastic substrate and the tablet surface area of ​​1 mm2 is measured. 2 For each tablet, 0.2 μL of water at 25° C. is dropped with a dropper, and the tablet is held in this state for 10 to 20 seconds, after which it can be measured by the following procedure. In the case of the plain tablet of the present invention, the maximum stress is preferably less than 20 N, more preferably 15 N or less, even more preferably 10 N or less, and particularly preferably 5 N or less. The procedure for measuring the maximum stress is as follows: A schematic diagram of the measurement device is shown in Figure 1. In Figure 1, reference numeral 1 denotes the tablet, reference numeral 2 denotes the slit, and reference numeral 3 denotes the silicone tube.

[0053] <Maximum stress measurement procedure> A silicone tube is arranged vertically and fixed so as to be movable in the vertical direction, and a pair of slits are fixed while sandwiching the silicone tube in the horizontal direction. One tablet is filled below the slit in the silicone tube, and the silicone tube is moved 20 mm upward along the slit at a speed of 0.5 mm / s relative to the tablet, and the maximum stress is measured. The silicone tube used in the measurement has a cross-sectional area that is smaller than that of the tablet and greater than 40% of that of the tablet. The ratio of the cross-sectional area of ​​the tablet to that of the silicone tube is preferably 40% to 60%, and more preferably 45% to 55%.

[0054] The above-mentioned "up-down direction" refers to a direction perpendicular to a horizontal plane. The above-mentioned "left-right direction" refers to a direction perpendicular to the up-down direction. The above-mentioned "cross-sectional area of ​​the silicone tube" refers to the area of ​​the portion surrounded by the inner surface of the silicone tube in a cross section obtained by cutting the silicone tube in a direction perpendicular to its longitudinal direction when no tablet is filled. The cross-sectional area of ​​the tablet refers to the area of ​​the largest cross section of the tablet when it is packed in the silicone tube and cut along a plane perpendicular to the longitudinal direction of the silicone tube.

[0055] Furthermore, the disintegration time of the plain tablet of this embodiment when water is used as a solvent is within 60 minutes, preferably within 40 minutes, and more preferably within 20 minutes. The lower limit of the disintegration time is, for example, 1 minute or more, which facilitates tablet production. The disintegration time refers to the time it takes for a sample in a solvent to disintegrate. The procedure for measuring the disintegration time follows the method described in "Disintegration Test Method" in Section "6.09" of the Japanese Pharmacopoeia, 15th Edition. When using tablets with a diameter of 3 to 15 mm, a thickness of 4 to 7 mm, and a weight of 150 to 500 mg, it is preferable to use a disintegration tester manufactured by Toyama Sangyo Co., Ltd., Model No. NT-400. The disintegration time relative to the tablet thickness of the tablet of this embodiment is preferably 0.01 min / mm or more and 25 min / mm or less, more preferably 0.05 min / mm or more and 20 min / mm or less, even more preferably 0.1 min / mm or more and 12 min / mm or less, even more preferably 0.15 min / mm or more and 8 min / mm or less, and most preferably 0.2 min / mm or more and 4 min / mm or less.

[0056] <Measuring procedure for disintegration time> One tablet is placed in each of six glass tubes in a disintegration tester. Each glass tube is open at the top and bottom, and a stainless steel mesh with a mesh size of 1.8 mm to 2.2 mm is attached to the bottom of the glass tube. The glass tube containing the tablets is placed in water at 37±2°C, and the disintegration tester is started. The glass tube in the disintegration tester is observed, and when it is confirmed that the tablets are about to disintegrate, the glass tube is pulled out and the disintegration state of the tablets is observed. This process is repeated until the tablets are completely disintegrated. The time from when the disintegration tester is started to when all six tablets have disintegrated is measured, and this measured time is taken as the disintegration time. The tablets are considered to have disintegrated when no tablet residue is found in the glass tube, or if any is found, it is a soft substance that clearly does not retain its original shape.

[0057] 5. Manufacturing method A suitable method for producing the core tablet of this embodiment will be further described below. The manufacturing method of this embodiment involves tableting a raw material powder containing a gelling agent and one or more (specific excipients) selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates. Examples of gelling agents, sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates include those mentioned above. Furthermore, components other than the gelling agent and specific excipient in the powder containing the gelling agent and specific excipient include the above-mentioned excipients, disintegrants, binders, lubricants, emulsifiers, active ingredients, seasonings, fragrances, etc. The preferred ranges of the mass proportion of the gelling agent in the raw powder, the preferred mass proportions of the preferred gelling agent components, the preferred mass proportions of the specific excipients, and the preferred mass proportions of the excipients, disintegrants, and lubricants are the same as the preferred mass proportions of these in the above-mentioned plain tablets.

[0058] As mentioned above, the plain tablet may be either a core-coated one or a core-less one. In the case of a core-coated one, a raw material powder containing any core is compressed into tablets.

[0059] The raw powder containing a gelling agent and a specific excipient may be a mixture of a powdered gelling agent, a powdered specific excipient, and other powdered ingredients that are included as needed, or may be a granulated powder obtained by granulating a mixture of a powdered gelling agent, a powdered specific excipient, and other powdered ingredients that are included as needed. As the granulation method, any known granulation method used in producing oral tablets by granulation tableting can be used without any particular limitation.

[0060] The method for producing tablets having a plain tablet of the present invention preferably includes a step of mixing a powder of a gelling agent with one or more powders selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates, and a step of compressing the resulting mixed powder into tablets without spraying an aqueous solution of a gelling agent. As described above, this is because a plain tablet in which a gelling agent is uniformly mixed with a specific excipient is superior in terms of disintegration and sliminess, particularly disintegration, compared to a plain tablet obtained by compressing particles containing a sugar alcohol and a gelling agent whose surfaces are coated with a gelling agent.

[0061] As described above, the tablet having the plain tablet of this embodiment is preferably a compressed product of a mixed powder containing a gelling agent and a specific excipient, particularly a compressed product obtained by compressing the mixed powder obtained without spraying an aqueous solution containing a gelling agent, because it is easy to obtain a plain tablet in which the gelling agent is present over the entire surface. Even if the expressions "compressed product of a mixed powder containing a gelling agent and a specific excipient" and "compressed product obtained by obtaining a mixed powder (containing a gelling agent and a specific excipient) without spraying an aqueous solution containing a gelling agent and compressing the mixed powder" included the manufacturing method, it was not realistic to specify the presence form of the gelling agent and the specific excipient in the plain tablet in more detail than described in this specification, and there were impossible circumstances that forced the use of such expressions.

[0062] As described above, the tablet having a bare tablet of this embodiment contains a gelling agent, so that during storage it has the same hard properties as a tablet having a bare tablet that does not contain a gelling agent. However, when taken, when it comes into contact with a liquid medium such as water, its surface gels, giving it a slimy feel, flexibility, and elasticity, making it easy to swallow. Furthermore, when it comes into contact with a liquid medium such as water, the shape of the bare tablet portion is maintained, and the active ingredients present in the bare tablet portion are prevented from dissolving in the oral cavity. Thus, the tablet of this embodiment has the characteristic of swelling in a liquid medium such as water, causing a slimy feel on the surface of the bare tablet.

[0063] 6. Preferred Embodiments of the Present Invention Preferred embodiments of the present invention include, for example, the following. A gelling agent; Tablets having a plain tablet containing one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates (excluding tablets obtained by compressing particles granulated by spraying an aqueous solution in which a gelling agent has been dissolved).

[0064] A gelling agent; A tablet having a plain tablet containing one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch hydrolysates (excluding those containing crospovidone, carboxymethyl starch sodium, croscarmellose sodium, or low-substituted hydroxypropyl cellulose).

[0065] A gelling agent; A tablet having a plain tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starch and starch hydrolysates.

[0066] one or more selected from locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, gum arabic, gum ghatti, tragacanth gum, karaya gum, cassia gum, rhamsan gum, welan gum, macrophomopsis gum, curdlan, pullulan, gellan gum, polyamino acids, polylactic acid, and salts and derivatives thereof; A tablet having a plain tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starch, and starch hydrolysates.

[0067] one or more selected from locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, gum arabic, gum ghatti, tragacanth gum, karaya gum, cassia gum, rhamsan gum, welan gum, macrophomopsis gum, curdlan, pullulan, gellan gum, polyamino acids, polylactic acid, and salts and derivatives thereof; One or more selected from xanthan gum, guar gum, alginic acid, and carrageenan, A tablet having a plain tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starch, and starch hydrolysates.

[0068] A gelling agent; Disaccharides, A tablet having a plain tablet containing one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch, and starch hydrolysates.

[0069] A gelling agent; Sugar alcohols and and one or more selected from starch and pregelatinized starch, A tablet having a plain tablet that does not contain a coating layer of a gelling agent. [Example]

[0070] The present invention will be described in more detail below with reference to examples. However, the scope of the present invention is not limited to these examples. Commercially available products were used as the materials listed in Tables 1-3. In particular, Isomalt 900P manufactured by Showa Sangyo Co., Ltd. was used as the isomaltooligosaccharide. KC Flock W-400G manufactured by Nippon Paper Industries Co., Ltd. was used as the crystalline cellulose. Calcium carboxymethylcellulose with an etherification degree of 0.5 to 0.7 mol / C6 was used as the carboxymethylcellulose. Perfiller 102 manufactured by Freund Corporation was used as the starch powder. Non-GMO Corn Alpha-Y manufactured by Sanwa Starch Industry Co., Ltd. was used as the pregelatinized starch. Max 1000 manufactured by Matsutani Chemical Industry Co., Ltd. was used as the dextrin.

[0071] 1. Evaluation of sliminess Example 1 For the raw powder, 400 tablets of various raw materials (except calcium stearate) were mixed in a plastic bag according to the composition ratios shown in Table 1, then passed through a sieve, and calcium stearate was added and mixed. This mixed powder was directly compressed using a rotary tablet press (Kikusui Seisakusho) to obtain disc-shaped plain tablets. The hardness of the resulting plain tablets was measured using a Schleuniger tablet hardness tester. The tablet diameter and thickness of the resulting plain tablets were measured using a digital caliper (Digimatic Caliper CD-15AX; Mitutoyo). The hardness was 7.4 kgf, the tablet diameter was 10 mm, and the tablet thickness was 3.52 mm. The weight of one of the resulting plain tablets was measured and found to be 270 mg. The hardness, tablet diameter, tablet thickness, and weight are the average values ​​measured for three tablets.

[0072] Example 2 Plain tablets were obtained in the same manner as in Example 1, except that the blending ratio of the raw material powders was changed according to the blending ratio in Table 1. The obtained plain tablets were subjected to the same measurements as in Example 1, and the hardness was 7.7 kgf, the tablet diameter was 10 mm, the tablet thickness was 3.50 mm, and the weight was 270 mg.

[0073] [Evaluation of Examples 1 and 2] For the plain tablets obtained in Examples 1 and 2, measurements of the myoelectric potential of the throat at the time of administration and a questionnaire on the administration sensation were conducted in a single-blind crossover study. In addition, the time it took for the tablet to slide down an incline was measured to evaluate its slipperiness.

[0074] How to take the uncoated tablets The subjects were six healthy adults (male to female ratio 2:4) who were aware that they had difficulty swallowing tablets. The dosage was as follows: first, four tablets were placed in the mouth, then 20 mL of water at 22°C was placed in the mouth, and the tablets were then swallowed together with the water.

[0075] -Electromyography The electromyographic potential was measured using an electromyographic device (AM Science Corporation's wireless electromyographic measurement and analysis system "Lateo"). The measurement method followed the instructions in the manual provided with the electromyographic device, specifically as follows: The electrodes of the electromyographic device were attached to the throat, and the subjects were instructed to ingest 20 mL of water, the same amount as when taking the uncoated tablets, to allow their throats to acclimate. Next, the electromyographic potential of the throat was measured after taking 20 mL of water. After placing four uncoated tablets in the mouth, the electromyographic potential of the throat was measured after taking the tablets with 20 mL of water for each test group. The amount of muscle activity was calculated from the integral calculated based on the electromyographic potential (unit: volts (V)), relative to the amount of muscle activity when only water was taken, which was set at 100%. The relative values ​​per person were summed and divided by the number of people to obtain the amount of muscle activity (%). In Figures 1 to 3, one count is 1 / 200 second. Measurements in each test group were conducted after a rest period of approximately 5 minutes, and the order in which the tablets were taken was changed for each subject.

[0076] ·questionnaire Slipperiness was evaluated on a 7-point scale, with the lowest rating (-3 points) being a tablet that was difficult to swallow because it was not slippery enough to get stuck when swallowed and did not move down the throat, and the highest rating (3 points) being a tablet that was easy to swallow because it was slippery enough that no friction was felt in the throat and did not get stuck in the throat. Stickiness was rated on a 7-point scale, with the lowest rating (-3 points) being when the product was sticky enough to stick to the tongue or pharynx, making it difficult to drink, and the highest rating (3 points) being when the product was not sticky enough to stick to the tongue or pharynx, and was easy to drink, with only a slimy feel.

[0077] Slope sliding time A U-shaped aluminum channel (straight in side view, 90 cm long, 1.2 cm wide) was inclined at a 30° angle and fixed, and 150 ml of water was supplied from the top of the channel at a rate of 150 ml per minute. In this state, a single plain tablet was slid down the channel from a position 10 cm below the top end of the channel, and the time (seconds) required for it to slide 80 cm to the bottom end was measured. The test was performed five times, and the average of the five measurements was calculated to obtain the slope sliding time (seconds).

[0078] The amount of throat muscle activity (%) obtained by myoelectric potential measurement is shown in Table 1, and representative electromyograms are shown in Figures 2 to 4. The average evaluation scores of six people obtained from the questionnaire and the measurement results of the time (seconds) required to slide down a slope are shown in Table 1. In Table 1, the unit of composition of the plain tablet is parts by mass.

[0079] [Table 1]

[0080] As is clear from Table 1 and Figures 2 to 4, the plain tablets of Examples 1 and 2 suppressed the increase in throat muscle activity to about 1.5 times compared with when only water was taken, making them easy to swallow without requiring force and causing little swallowing stress. The questionnaire also showed that while the tablets were perceived as slippery, they were easy to swallow without sticking to the tongue or pharynx. In addition, the plain tablets containing crospovidone, carboxymethyl starch sodium, croscarmellose sodium or low-substituted hydroxypropyl cellulose exhibited reduced slipperiness and less stickiness compared to those of Examples 1 and 2.

[0081] Furthermore, when comparing the time it took to slide down a slope, as shown in Table 1, Examples 1 and 2 slid down in 2 seconds or less, which indicates that the plain tablets of the Examples become more slippery when in contact with water, making them easier to swallow. In addition, the plain tablets containing crospovidone, carboxymethyl starch sodium, croscarmellose sodium or low-substituted hydroxypropyl cellulose have a lower slope sliding property than those of Examples 1 or 2.

[0082] As a result of the above, in the case of uncoated tablets containing a gelling agent and specific excipients (sugar alcohol, pregelatinized starch), even people who have difficulty swallowing tablets can take them easily with little resistance.

[0083] 2. Evaluation of disintegration Examples 3 to 6 According to the compounding ratio in Table 1 below, plain tablets were obtained in the same manner as in Example 1, except that the hardness was changed to 9 kgf, the tablet diameter to 9 mm, the tablet thickness to 4.81 to 5.08 mm (4.81 mm in Example 3, 4.89 mm in Examples 4 and 6, and 5.08 mm in Example 5), and the weight was changed to 300 mg. The disintegration time of the obtained plain tablets was measured by the following method, and the results are shown in Table 2.

[0084] Collapse time The disintegration time was measured using a disintegration tester (Toyama Sangyo Co., Ltd., model number: NT-40H) according to the method described in "Disintegration Test Method" in the 15th Edition of the Japanese Pharmacopoeia, item "6.09" with n = 6. Water was used as the solution.

[0085] The units for the compositions in Table 2 are parts by mass.

[0086] [Table 2]

[0087] As is clear from Table 2, plain tablets containing a gelling agent and a specific disintegrant (sugar alcohol, cellulose, cellulose derivatives, starch) had a short disintegration time. Even when a specific disintegrant (crospovidone) was added, the disintegration time was only reduced by about 20% compared to when no disintegrant was added.

[0088] 3. Evaluation of sliminess and disintegration time [Examples 7 to 14, 16 to 21, Comparative Example 1] According to the blending ratios in Table 3 below, plain tablets were obtained in the same manner as in Example 1. The obtained plain tablets of Examples 7 to 14, 16 to 21 and Comparative Example 1 had similar hardness, tablet diameter and tablet thickness to those of Examples 3 to 5, and weighed 300 mg.

[0089] Example 15 57.1 parts by mass of sorbitol and 30.0 parts by mass of maltose were placed in a fluidized bed granulator (fluidized bed granulator, drying and coating machine, model: FD-LAB-1, Powrex Corporation), and a suspension of crystalline cellulose was sprayed onto the mixture. After that, a suspension of xanthan gum diluted with hot water to a concentration of 0.1% (w / v) was sprayed onto the mixture to granulate the mixture. This yielded a particle composition (particles containing a sugar alcohol and a gelling agent, the surfaces of which were coated with a gelling agent) in which a coating layer of xanthan gum was formed on the surface of particles made of a mixed powder of sorbitol and maltose. The obtained particle composition was mixed with 0.5 parts by mass of calcium stearate and then tableted using a rotary tablet press (Kikusui Seisakusho) to obtain plain tablets weighing 300 mg whose hardness, tablet diameter, and tablet thickness were similar to those of Examples 3 to 5. The amounts of crystalline cellulose and xanthan gum in the plain tablets were as shown in Table 1.

[0090] The disintegration times of the plain tablets obtained in Examples 7 to 21 and Comparative Example 1 were measured in the same manner as in Examples 3 to 6. The results are shown in Table 3.

[0091] Furthermore, the maximum stress was measured for the plain tablets obtained in Examples 7 to 21 and Comparative Example 1 by the following method.

[0092] <Maximum stress measurement procedure> The tablet was placed on a plastic substrate and the surface area of ​​the tablet was 1 mm 2 0.2 μL of water at 25° C. was dropped onto the sample with a dropper, and the sample was kept in this state for 15 seconds. A silicone tube with an inner diameter of 9 mm and an outer diameter of 11 mm was placed vertically so that its longitudinal direction coincided with the vertical direction and was fixed so that it could be moved vertically. A pair of slits were fixed in a state in which the silicone tube was sandwiched between them in the left-right direction. One of the above-mentioned plain tablets (tablet diameter 9 mm) was filled below the slit in the silicone tube. The silicone tube was moved 20 mm upward along the slit relative to the plain tablet at a speed of 0.5 mm / s, and the maximum stress was measured using a creep meter (RE2-33005C) manufactured by Yamaden Co., Ltd. The cross-sectional area of ​​the silicone tube used for the measurement was 50% of the cross-sectional area of ​​the plain tablet. When the stress exceeded 20, the measurement was terminated at that point. The silicone tube used was a clear silicone square tube manufactured by Fuso Rubber Industries Co., Ltd. The slits were made using a special cylindrical extrusion jig (AT-43446) manufactured by Yamaden Co., Ltd., and were fixed in a position where the minimum spacing between them was 2 mm. The maximum stress was calculated as the average of three replicates.

[0093] The units for the compositions in Table 3 are parts by mass. [Table 3]

[0094] As can be seen from the comparison between Examples 7 to 21 and Comparative Example 1 in Table 3, the maximum stress is significantly lower in the plain tablets of Examples 7 to 21, which contain a gelling agent and a specific excipient, than in the plain tablet of Comparative Example 1, which contains only a specific excipient and no gelling agent. Furthermore, the results of Examples 7 to 14 show that the maximum stress is particularly low in the case of plain tablets containing, among specific excipients, monosaccharides, disaccharides, oligosaccharides or starch hydrolysates.

[0095] Furthermore, a comparison of Examples 15 and 16 reveals that the plain tablets obtained by compressing particles containing a sugar alcohol and a gelling agent, the surfaces of which are coated with a gelling agent, have a shorter disintegration time and a lower maximum stress.

[0096] In addition, compared to plain tablets obtained by tableting particles containing a sugar alcohol and a gelling agent whose surfaces are coated with a gelling agent, plain tablets obtained by tableting a sugar alcohol mixed with a gelling agent tend to have a shorter disintegration time and lower maximum stress, and this tendency is observed not only when sorbitol is used as the sugar alcohol, but also when sugar alcohols other than sorbitol (such as erythritol and mannitol) are used.

[0097] Furthermore, the results of Examples 17 to 21 show that when locust bean gum is used as a gelling agent, the disintegration time is particularly short and the maximum stress is low, making locust bean gum particularly superior among gelling agents in terms of achieving both disintegration and sliminess.

[0098] The following plain tablets (Formulation Examples 1 to 41) were produced in the same manner as in Example 1. All of the plain tablets had excellent slipperiness and disintegration properties. In particular, plain tablets combining two or more gelling agents, plain tablets containing one or more selected from monosaccharides, disaccharides, oligosaccharides, starch derivatives, and starch hydrolysates, plain tablets containing a combination of two or more components belonging to different categories of specific excipients, and plain tablets combining disaccharides with one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch, and starch hydrolysates had excellent slipperiness and disintegration properties. In addition, tablets prepared in Formulation Examples 1 to 41 by coating the plain tablets with sucrose and adjusting the proportion of the surface area of ​​the tablet covered by the coating layer to 20% or more but less than 30% (the coating proportion was adjusted by applying sucrose using water) also had excellent slipperiness and disintegration properties. Similarly, the plain tablets prepared so that the proportion of the tablet surface area covered by the coating layer was 5% or more and less than 10% also had excellent sliminess and disintegration properties.

[0099] [Table 4]

[0100] [Table 5]

[0101] [Table 6]

[0102] [Table 7] [Explanation of symbols]

[0103] 1 tablet 2 slits 3 silicone tubes [Industrial Applicability]

[0104] The tablets having the uncoated tablets of the present invention are easy to swallow, and do not require coating of the entire surface, so that the increase in size due to coating can be avoided, and the absence of coating can reduce production costs. They also have excellent ease of disintegration after ingestion. Therefore, it is clear that the tablets having the uncoated tablets of the present invention can be used or manufactured as supplements, health foods, nutrient-functional foods, functional foods, foods for specified health uses, and pharmaceuticals, and are useful.

Claims

[Claim 1] The invention described in the specification.

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