JP7745283B2 - Tablets and tablet manufacturing method - Google Patents

Description

The present invention relates to tablets and their manufacturing methods.

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 is often difficult for people who have difficulty swallowing tablets, and especially for children and elderly people with poor swallowing function.
To make tablets easier to swallow, it is necessary to improve the tablet's slipperiness, the resistance to 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 is still large, and the effect of improving swallowing is not sufficient.

Japanese Patent Application Publication No. 11-60472 Special Publication No. 2011-502132 Special table 2014-534977 publication

The present invention aims to provide a tablet that can be taken easily with little resistance, even by people who have difficulty swallowing tablets. Furthermore, conventional coated tablets tend to increase in volume due to the coating layer, and coating the tablet surface after tableting increases labor and manufacturing costs. However, the present invention aims to prevent tablets from becoming too large, and to provide a tablet that is easy to swallow and also reduces manufacturing costs.

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.

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 core tablet.

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, becomes elastic, and the surface of the tablet having a slimy feel is created, 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.

FIG. 1 is a conceptual diagram of a method for measuring maximum stress. FIG. 2 shows the electromyogram when only water was taken. FIG. 3 shows an electromyogram when the tablet produced in Example 1 was taken. FIG. 4 shows an electromyogram when the tablet produced in Example 2 was taken.

The present invention will now be described based on its preferred embodiments.

The tablet of the present invention comprises 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 without a coating layer formed on its surface. In this specification, "a tablet having a bare tablet" refers to a tablet having a portion on its surface without a coating layer, and such portion is in a bare tablet state (hereinafter, the portion on the tablet surface without a coating layer is referred to as the bare tablet portion). Furthermore, in this specification, "bare tablet" refers to a tablet having substantially no coating layer formed on its surface (a tablet in which the proportion of the area covered by the coating layer to the total surface area of the tablet is less than 5%). In this specification, "bare tablet" is a concept that is encompassed by "tablet having a bare tablet."

The tablet having a bare tablet of this embodiment exhibits a slimy property (also referred to as slipperiness) when the bare tablet portion comes into contact with a liquid medium such as water. The tablet having a bare tablet of this embodiment preferably has a gelling agent on the outermost surface of the bare tablet portion. The outermost surface refers to the portion located on the surface side of the bare tablet portion, and refers to a range of 0 mm to 1 mm from the surface of the bare tablet portion toward the center. By having a gelling agent on the bare tablet portion of this embodiment, particularly on the outermost surface of the bare tablet portion, the tablet becomes slimy on the surface of the bare tablet portion when it comes into contact with a liquid medium such as water. This makes the tablet having a bare tablet of this embodiment easy to swallow even without a coating layer. It is particularly preferable that the tablet having a bare tablet have a gelling agent on the entire outermost surface of the bare 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 bare tablet portion, it can be said that the gelling agent is present on the entire outermost surface of the bare tablet portion. The presence of a gelling agent on the surface can be confirmed by scraping off approximately 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 described below, tablets having a gelling agent on the entire outermost surface of the outermost tablet portion can be easily obtained by compressing a mixed powder containing a gelling agent and specific excipients.

In the case of a tablet having a bare tablet of the present invention, the bare tablet portion preferably exists on the outermost surface of the tablet, since the effect of the gelling agent is exerted by the bare tablet portion. Specifically, the proportion of the surface area occupied by the bare 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 a tablet having a bare tablet of the present invention has a coating layer, the proportion of the tablet's surface area 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 tablet's surface area covered by the coating layer is less than 5%). Furthermore, when a tablet having a bare tablet of the present invention has a coating layer, the thickness of the coating layer from the surface of the bare 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 more easily exerted, production costs can be reduced, and the tablet size can be prevented from increasing. When the coating layer covers only part of the tablet, the coating layer may be present continuously but unevenly distributed in a single area, or may be dispersed in an island pattern. For example, if a powdered substance other than a gelling agent (e.g., sugars or other seasonings) is sprinkled on the surface of the plain tablet, resulting in a coating layer on only part of the tablet surface, this is acceptable because the gelling agent present in the plain tablet portion is effective.

A tablet having a core may have a structure in which the surface portion is differentiated from the portion closer to the center, or it may not have such a structure. For example, a tablet having a core may have a multi-layer structure like a dry-coated tablet. In particular, a tablet having a core does not have a multi-layer structure, and is a single-layer structure, which is preferable in terms of ease of production, etc.

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 on the outermost surface of a tablet having a naked tablet, but a gelling agent may be present in a location other than the outermost surface. For example, a tablet having a naked tablet may contain a gelling agent in both the outermost surface and the portion closer to the center (also referred to as the center). 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 and the composition of the center may be the same or different, but being the same is preferable from the perspective 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 the tablet having a naked tablet in half with a cutter or the like, scraping off about 30 mg of the tablet at any location more than 1 mm from the surface of the tablet having a naked tablet 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 below as disintegrants are not included in the gelling agent in this application.

The gelling agent 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. A single gelling agent may be used alone, or two or more may be used in combination.

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 disintegrated in the body after ingestion. In particular, the inclusion of locust bean gum is preferred, as it not only provides excellent ease of disintegration after ingestion, but also exhibits a high level of both disintegrability and sliminess.

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

In a tablet having a core tablet, the proportion of gelling agent is preferably 0.01% by mass or more to sufficiently generate a slimy feeling when contacted with a liquid medium such as water. Furthermore, in terms of ease of dissolution of the active ingredient, the proportion of gelling agent in a tablet having a core tablet is preferably 70% by mass or less. From these perspectives, 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 a tablet having a core tablet of this embodiment contains at least one selected from the specific gelling agents described above, 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 described above. 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 containing the core tablet contains only one type selected from the specific gelling agents, and refers to the total mass of those types when the tablet containing the core tablet contains two or more types.

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

For example, when a tablet having a core 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 core tablet is 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, from the viewpoint of increasing the slipperiness and the content of the active ingredient, 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.

Furthermore, when the plain tablet of the present invention contains guar gum and locust bean gum, the ratio of the former to the latter in the plain tablet is more preferably 10 to 1,000 parts by mass of locust bean gum per 100 parts by mass of guar gum, even more preferably 15 to 900 parts by mass, and particularly preferably 20 to 800 parts by mass, in order to enhance the slipperiness and the content of the active ingredient.

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

As described above, a plain tablet may contain one or more components 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.

Sugar alcohols include monosaccharide alcohols, disaccharide alcohols, and trisaccharide or higher sugar 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 sugar alcohols include maltotriitol, isomaltotriitol, and panitol. From the standpoint of manufacturability, such as ensuring sufficient tablet hardness after compression, the sugar alcohol is preferably at least one selected from disaccharide alcohols, and particularly preferably at least one selected from reduced maltose and reduced palatinose.

Monosaccharides include glucose, galactose, fructose, and mannose. Of these, glucose is preferred because it is readily available and combines disintegrating properties with slimy properties.

Disaccharides include sucrose, maltose, lactose (milk sugar), trehalose, turanose, and cellobiose. Of these, one or more selected from trehalose, sucrose, and maltose are preferred from the standpoint of achieving both disintegrability and sliminess, with sucrose and maltose being particularly preferred. While the effects of the present invention can be achieved even when lactose is included, from the standpoint of achieving both disintegrability and sliminess, it is more preferred that the disaccharide be a disaccharide other than lactose.

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

It is preferable for tablets having a bare tablet to contain either monosaccharides, disaccharides, or oligosaccharides, not only from the viewpoint of taste masking but also from the viewpoint of promoting saliva secretion. It is particularly preferable for the surface of the bare tablet to contain these sugars.

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 then purifying it. Examples include the crystalline cellulose described in the 15th Revised Japanese Pharmacopoeia Commentary (published by Hirokawa Shoten). Crystalline cellulose can be classified into crystalline cellulose powder and crystalline cellulose complex, and either of these can be used for the plain tablets of the present invention.

Cellulose derivatives include carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and methylcellulose. Carboxymethylcellulose with an etherification degree of 0.2 mol/C6 to 1.0 mol/C6 is preferred from the standpoint of availability and achieving both sliminess and disintegration time, with 0.5 mol/C6 to 0.8 mol/C6 being even more preferred. The effects of the present invention can be achieved even when the composition contains croscarmellose sodium, which is internally crosslinked with carboxymethylcellulose sodium, or low-substituted hydroxypropylcellulose. However, from the standpoint of achieving both disintegration and sliminess, cellulose derivatives other than croscarmellose sodium and low-substituted hydroxypropylcellulose are more preferred.

Examples of starch include natural starch. Starch can be derived from corn, potato, arrowroot, tapioca, sweet potato, rice, wheat, barley, yam, taro, etc. When incorporating starch, it is preferable to incorporate it in combination with a sugar alcohol, as this will achieve both disintegration and slimy properties.

Starch derivatives include modified starch, oxidized starch, enzyme-treated starch, pregelatinized starch, starch phosphate, distarch phosphate, starch acetate, starch octenylsuccinate, 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 while the effects of the present invention can be achieved even when sodium carboxymethyl starch is included, from the perspective of achieving both disintegration and sliminess, starch derivatives other than sodium carboxymethyl starch are more preferred.

Examples of starch hydrolysates include dextrin, preferably one with a DE of 8 to 9.5.

The content of the specific excipient in the tablet having a core tablet is preferably 10 parts by mass or more per 100 parts by mass of gelling agent in the tablet having a core tablet, in order to further enhance the effect of using the gelling agent and the specific excipient in combination. The amount of the specific excipient is preferably 3,000 parts by mass or less per 100 parts by mass of gelling agent in the tablet having a core tablet, in order to increase the content of the active ingredient. From these points of view, the amount of the specific excipient in the tablet having a core tablet is preferably 10 to 3,000 parts by mass, more preferably 20 to 2,500 parts by mass, and particularly preferably 30 to 2,000 parts by mass, per 100 parts by mass of gelling agent in the tablet having a core tablet.

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

The plain tablet of the present invention preferably contains one or more specific excipients selected from monosaccharides, disaccharides, oligosaccharides, starch derivatives (particularly pregelatinized starch), and starch hydrolysates, as these excipients have a high degree of sliminess, and it is even more preferable for the tablet to contain a monosaccharide, disaccharide, oligosaccharide, or starch hydrolysate.

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.

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

In addition, from the viewpoint of improving disintegrability and sliminess, it is preferable for tablets having a plain tablet to contain, as the specific excipient, a combination of a disaccharide and one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch, and starch hydrolysates, and a combination of a disaccharide and an oligosaccharide or a cellulose derivative is particularly preferred. When tablets having a plain tablet contain, as the specific excipient, a combination of a disaccharide and another specific excipient, from the viewpoint of achieving both sliminess and disintegrability, the other specific excipient is preferably present in an amount of 1 part by mass to 1,000 parts by mass, more preferably 5 parts by mass to 300 parts by mass, and particularly preferably 5 parts by mass to 100 parts by mass per 100 parts by mass of the disaccharide.

In addition, from the viewpoint of improving disintegrability and sliminess, it is preferable for tablets having a plain tablet to contain a combination of a sugar alcohol and starch or pregelatinized starch as the specific excipient. When a tablet having a plain tablet contains a combination of a sugar alcohol and starch or pregelatinized starch as the specific excipient, from the viewpoint of achieving both sliminess and disintegrability, the amount of starch or pregelatinized starch per 100 parts by mass of sugar alcohol is more preferably 10 to 1,000 parts by mass, even more preferably 30 to 700 parts by mass, and particularly preferably 50 to 500 parts by mass.

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 tablets that are 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 starch and at least one selected from 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.

It is preferable that tablets having a plain tablet contain a specific excipient in the outermost surface portion of the plain tablet portion, and it is also preferable that the core portion also contains a specific excipient.

3. Other components 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.

It is preferable for tablets having a plain tablet to contain a lubricant in order to improve manufacturability (to prevent punch sticking during tableting). Examples of lubricants include magnesium stearate and calcium stearate. When a lubricant is contained, its proportion 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.

The tablet having a core 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 core 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, i.e., is a tablet to be swallowed. Needless to say, the tablet of this embodiment may also be used as a supplement, health food, nutrient-functional food, food with functional claims, food for specified health uses, and pharmaceuticals.

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 mouth, thereby increasing the supply of liquid media such as water to the tablet. Examples of such seasonings include sweeteners and acidulants. Examples of sweeteners that can be used include sucralose sucrose derivatives, peptide sweeteners such as aspartame, alitame, neotame, and glycyrrhizin, as well as 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.

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, carboxymethyl starch sodium, croscarmellose sodium, and low-substituted hydroxypropyl cellulose. Although the effects of the present invention are achieved even when a disintegrant is contained, from the viewpoint of excellent slipperiness, a low content of disintegrant is preferable. 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 none, per 100 parts by weight of the tablet having a core tablet.

Among the disintegrants, from the viewpoint of excellent slipperiness, it is preferable that 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 low. Specifically, the amount of disintegrant per 100 weight parts of the plain tablet 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. Note that low-substituted hydroxypropyl cellulose is produced by reacting propylene oxide with alkali cellulose at high temperature, and when dried at 105°C for 1 hour, it contains 5.0 to 16.0% hydroxypropyl groups.

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. The effects of the present invention are achieved even when the tablet contains particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent. However, from the viewpoint of excellent disintegration properties, a lower content of particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent is preferable. 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 none. The particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent are formed by, for example, spraying the gelling agent onto particles containing the 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 instead the gelling agent and a specific excipient are uniformly mixed, thereby making it easier to shorten the disintegration time.

The absence of sugar alcohols and gelling agent-containing particles whose surfaces are coated with a gelling agent can be confirmed, for example, by examining the distribution of gelling agent in a tablet having a plain tablet using cross-sectional imaging such as TOF-SIMS. If no layer of locally concentrated gelling agent is observed and the gelling agent is uniformly dispersed throughout the tablet, it can be said that the tablet having a plain tablet of the present invention does not contain sugar alcohols and gelling agent-containing particles whose surfaces are coated with a gelling agent.

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 or more and 500 mg or less, more preferably 120 mg or more and 450 mg or less, and most preferably 150 mg or more and 400 mg or less. The diameter is preferably 5 mm or more and 12 mm or less, more preferably 5.5 mm or more and 11 mm or less, and most preferably 6 mm or more and 10 mm or less. The thickness is preferably 2 mm or more and 10 mm or less, more preferably 2.5 mm or more and 9 mm or less, and most preferably 3 mm or more and 8 mm or less. The hardness is preferably 3 kgf or more and 20 kgf or less, more preferably 4 kgf or more and 18 kgf or less, and most preferably 5 kgf or more and 16 kgf or less. The diameter, thickness, and hardness can be measured by the method described below.

Furthermore, for the tablet having a core tablet of the present invention, the maximum value of stress (maximum stress) generated when the tablet moves through a silicone tube can be measured by the method described below. Specifically, the tablet is placed on a plastic substrate, and 0.2 μL of water at 25°C is dropped with a dropper ^per 1 mm2 of the tablet surface area. After maintaining this state for 10 to 20 seconds, measurement can be performed using the following procedure. For the tablet having a core 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 measuring device is shown in Figure 1. In Figure 1, reference numeral 1 denotes a tablet, reference numeral 2 denotes a slit, and reference numeral 3 denotes a silicone tube.

<Procedure for measuring maximum stress>
Using a silicone tube arranged vertically and fixed so as to be movable vertically, and a pair of slits fixed in a state sandwiching the silicone tube in the left-right 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/sec relative to the tablet, and the maximum stress is measured. Note that the silicone tube used in the measurement has a cross-sectional area smaller than that of the tablet but 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%, more preferably 45% to 55%.

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.

The tablets of this embodiment, including the plain tablet, have a disintegration time in water as the solvent of 60 minutes or less, preferably 40 minutes or less, and more preferably 20 minutes or less. The lower limit of the disintegration time is, for example, 1 minute or more, which facilitates tablet production. Disintegration time refers to the time it takes for a sample in a solvent to disintegrate. The disintegration time is measured according to 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.

<Procedure for measuring 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 opening 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 state of disintegration 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.

5. Manufacturing Method A suitable manufacturing method for 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.

As mentioned above, the plain tablets may be either core-coated or core-less. In the case of core-coated tablets, raw powder containing any core is used as the raw material powder and compressed into tablets.

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.

The method for producing tablets having a plain tablet of the present invention preferably includes the steps 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 compressing the resulting mixed powder into tablets without spraying an aqueous solution of a gelling agent. This is because, as described above, plain tablets in which a gelling agent is uniformly mixed with a specific excipient are superior in terms of disintegration and sliminess, particularly disintegration, compared to plain tablets obtained by compressing particles containing a sugar alcohol and a gelling agent whose surfaces are coated with a gelling agent.

As described above, the tablets comprising the plain tablet of this embodiment are preferably tablets made from a mixed powder containing a gelling agent and a specific excipient, particularly tablets made by compressing such a mixed powder obtained without spraying an aqueous solution containing a gelling agent, because this makes it easy to obtain plain tablets in which the gelling agent is present over the entire surface. Even if the expressions "a compressed mixed powder containing a gelling agent and a specific excipient" and "a compressed mixed powder (containing a gelling agent and a specific excipient) obtained without spraying an aqueous solution containing a gelling agent and then compressed into tablets" included the manufacturing method, it would be unrealistic to specify the 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.

As described above, the tablet having a bare tablet of this embodiment contains a gelling agent, and therefore has the same hard properties as a tablet having a bare tablet without a gelling agent during storage. However, when taken, the surface gels upon contact with a liquid medium such as water, giving the tablet a slimy feel, flexibility, and elasticity, making it easier to swallow. Furthermore, when in 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. In this way, 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.

6. Preferred Embodiments of the Present Invention Preferred embodiments of the present invention include, for example, the following.
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 tablets obtained by compressing particles granulated by spraying an aqueous solution in which a gelling agent is dissolved).

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).

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

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.

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.

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

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.

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 for 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.

1. Evaluation of sliminess [Example 1]
For the raw material powder, 400 grains of various raw materials (excluding calcium stearate) were mixed in a plastic bag according to the blending ratios 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 obtained plain tablets was measured using a Schleuniger tablet hardness tester. Furthermore, the tablet diameter and thickness of the obtained plain tablets were measured using a digital caliper (Digimatic Caliper CD-15AX; Mitutoyo), and the hardness was 7.4 kgf, the tablet diameter was 10 mm, and the tablet thickness was 3.52 mm. Furthermore, the weight of one obtained plain tablet was measured and found to be 270 mg. The hardness, tablet diameter, tablet thickness, and weight are the average values measured for three tablets.

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.

[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.

- Method of taking plain tablets Six healthy adults who were aware that they had difficulty swallowing tablets were selected as subjects (male to female ratio 2:4). The method of taking the tablets was to first place four plain tablets in the mouth, then place 20 mL of water at 22°C in the mouth, and then swallow the plain tablets together with the water.

-Electromyographic potential measurement Electromyographic potential measurement was performed using an electromyograph (AM Scientific Corporation's wireless electromyographic measurement and analysis system "Lateo"). The measurement method followed the manual provided with the electromyograph, specifically as follows. The electrodes of the electromyograph were attached to the throat, and the subjects were asked to ingest 20 mL of water, the same amount as when taking the plain tablets, to allow the throat to acclimate. Next, the electromyographic potential of the throat was measured when 20 mL of water was taken. After that, four plain tablets were placed in the mouth, and the electromyographic potential of the throat when taken with 20 mL of water was measured for each test group. The amount of muscle activity was calculated from the integral calculated based on the obtained electromyographic potential (unit: volts (V)), and the relative value when the amount of muscle activity when only water was taken was set to 100 (%). The relative values per person were summed and divided by the number of people to obtain the amount of muscle activity (%). Note that in Figures 1 to 3, 1 Count is 1/200 seconds.
Measurements in each test group were conducted after a rest period of about 5 minutes, and the order in which the tablets were taken was changed for each subject.

- Questionnaire The slipperiness of the tablet 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 not go 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 it did not get stuck in the throat.
Stickiness was evaluated on a 7-point scale, with the lowest rating (-3 points) being when the tablet was sticky enough to stick to the tongue or pharynx, making it difficult to drink, and the highest rating (3 points) being when the tablet was not sticky enough to feel slimy and was easy to drink.

Slope sliding time 150 ml of water was supplied per minute from the top of an aluminum channel (linear in side view, channel length 90 cm, width 1.2 cm) with a U-shaped cross section inclined at 30° and fixed. In this state, one 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 value of the five measurements was calculated and used as the slope sliding time (seconds).

The muscle activity (%) of the throat 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 it took to slide down a slope (seconds) are shown in Table 1. In Table 1, the unit of composition of the plain tablet is parts by mass.

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 to 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.

Furthermore, when comparing the time 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.

As a result of the above, uncoated tablets containing a gelling agent and specific excipients (sugar alcohol, pregelatinized starch) can be taken easily with little resistance, even by people who have difficulty swallowing tablets.

2. Evaluation of disintegrability [Examples 3 to 6]
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 to 300 mg according to the compounding ratio in Table 1 below.
The disintegration time of the obtained plain tablets was measured by the following method, and the results are shown in Table 2.

Disintegration time: 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.

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

As is clear from Table 2, plain tablets containing a gelling agent and a specific disintegrant (sugar alcohol, cellulose, cellulose derivative, starch) had a short disintegration time. Furthermore, even when a specific disintegrant (crospovidone) was added, the disintegration time was only reduced by about 20% compared to tablets without a specific disintegrant.

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.

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/dryer/coating machine, model: FD-LAB-1, manufactured by Powrex Corporation), and a suspension of crystalline cellulose was sprayed onto the mixture. Then, 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, thereby obtaining 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 surfaces of particles made of a powder mixture 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.

The disintegration time of the plain tablets obtained in Examples 7 to 21 and Comparative Example 1 was measured using the same method as in Examples 3 to 6. The results are shown in Table 3.

Furthermore, the maximum stress was measured for the plain tablets obtained in Examples 7 to 21 and Comparative Example 1 using the method described below.

<Procedure for measuring maximum stress>
The plain tablet was placed on a plastic substrate, and 0.2 μL of water at 25° C. was added dropwise with a dropper per 1 mm ² of the surface area of the plain tablet, and the tablet was held in this state for 15 seconds.
A silicone tube with an inner diameter of 9 mm and an outer diameter of 11 mm was arranged 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 horizontally. One of the above-mentioned plain tablets (tablet diameter 9 mm) was filled below the slit in the silicone tube. The maximum stress when the silicone tube was moved 20 mm upward along the slit at a speed of 0.5 mm/s relative to the plain tablet 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 slit was a special cylindrical extrusion jig (AT-43446) manufactured by Yamaden Co., Ltd., which was fixed in a position where the minimum spacing between the slits was 2 mm.
The maximum stress was calculated as the average value of three replicates.

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

As can be seen from the comparison between Examples 7 to 21 and Comparative Example 1 in Table 3, the maximum stress is significantly reduced in the plain tablets of Examples 7 to 21, which contain a gelling agent and a specific excipient, compared to 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 monosaccharides, disaccharides, oligosaccharides or starch hydrolysates among the specific excipients.

Furthermore, a comparison of Examples 15 and 16 reveals that, compared to plain tablets obtained by compressing particles containing a sugar alcohol and a gelling agent whose surfaces are coated with a gelling agent, plain tablets obtained by mixing a sugar alcohol with a gelling agent and then compressing the mixture have a shorter disintegration time and a lower maximum stress.

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

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 an especially excellent gelling agent from the perspective of achieving both disintegration and sliminess.

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

1. Tablet 2. Slit 3. Silicone tube

The tablets having the uncoated form of the present invention are easy to swallow and do not require coating of the entire surface, which avoids the need for coating to increase the size of the tablets. Furthermore, not requiring a coating reduces manufacturing costs. They also disintegrate easily after ingestion. Therefore, it is clear that the uncoated tablets of the present invention are useful for use and manufacturing as supplements, health foods, foods with nutrient functions, foods with functional claims, foods for specified health uses, and pharmaceuticals.

Claims (2)

A swallowable tablet having a plain tablet containing a gelling agent and crystalline cellulose (excluding the following (A), (B), (C), (D), (E), (F) , (G) , (H), (I), (I), (I), (K), (K), (K), (K), (S), (S), (S), (S), (T), (T), (T), (T), (U ...
(a) a therapeutically active agent;
(b) a gelling agent comprising a heteropolysaccharide gum and a homopolysaccharide gum capable of cross-linking with each other when in contact with an environmental liquid, wherein the ratio of the heteropolysaccharide gum to the homopolysaccharide gum is 1:3 to 3:1;
(c) a pharmaceutically acceptable inert diluent selected from the group consisting of a pharmaceutically acceptable sugar, a polyhydric alcohol, an industrially produced direct compression diluent, and a mixture thereof; and (d) a pharmaceutically acceptable hydrophobic substance, wherein the ratio of the inert diluent (c) to the gelling agent (b) is 1:8 to 8:1,
A controlled-release solid dosage oral medication used to treat a disease in patients.
(A) A tablet containing 15 to 45% by mass of a thickening polysaccharide, 15 to 40% by mass of cellulose, 5 to 70% by mass of a water-soluble saccharide, and 0.2 to 10% by mass of a metal salt, and having a hardness of 15 to 70 N.
(c) A tablet containing 25% by mass of xanthan gum, 10% by mass of cellulose, 35.3% by mass of dextrin, 2.7% by mass of calcium chloride, and 22% by mass of lactose, and having a hardness of 39N.
(e) A tablet containing 50% by mass of xanthan gum, 20% by mass of cellulose, 5% by mass of potassium chloride, and 20% by mass of lactose, and having a hardness of 31N.
(E) In weight percent based on the final tablet weight,
(a) Cefadroxil monohydrate 50%;
(b) 10-12% of a mixture containing 87 parts by weight of microcrystalline cellulose and 13 parts by weight of guar gum;
(c) cross-linked polyvinylpyrrolidone 9.5-29%;
(d) colloidal silicon dioxide 2.5-10%;
(e) dibasic calcium phosphate 4-19%; and (f) mannitol or maltitol 9-21%. Uncoated tablets of cefadroxil monohydrate obtained by direct compression of an anhydrous pharmaceutical composition, which tablets can be orally administered to humans by swallowing, chewing, or disintegrating with water to form a drinkable suspension.
(K) An easily swallowable tablet characterized by blending (a) one or more members selected from the group consisting of carrageenan, sodium alginate, and xanthan gum, and (b) one or more members selected from the group consisting of crospovidone, sodium carboxymethyl starch, croscarmellose sodium, and low-substituted hydroxypropyl cellulose.
(K) A tablet consisting of 20% by mass of t-carrageenan, 10.0% by mass of crospovidone, 34.3% by mass of corn starch, 17.1% by mass of carboxymethylcellulose, 16.6% by mass of crystalline cellulose, 1.5% by mass of light anhydrous silicic acid, and 0.5% by mass of magnesium stearate, with a tablet weight of 290 mg, a hardness of 7.4 kgf, and a thickness of 3.345 mm.
(H) A tablet containing agar and/or gum arabic, which is obtained by premixing coenzyme Q10 with starch and then tableting the resulting composition with other ingredients.
(K) A matrix-type pharmaceutical tablet that can be administered orally once or twice a day by controlling the release of baclofen through gastric retention, comprising granules of baclofen and one or more diluents within a matrix that comprises at least a gelling agent, a gas generating agent, and a super-disintegrant.
(J) A tablet containing 6% by weight of baclofen, 10% by weight of xanthan gum, 10% by weight of microcrystalline cellulose and carboxymethylcellulose, 49.3% by weight of mannitol, 3% by weight of hydroxypropyl methylcellulose, 20.2% by weight of sodium bicarbonate, 0.5% by weight of precipitated silica, and 1% by weight of magnesium stearate.
(c) A tablet containing 6% by weight of baclofen, 24% by weight of mannitol, 7.5% by weight of xanthan gum, 10% by weight of sodium alginate, 7.5% by weight of crospovidone, 20% by weight of sodium bicarbonate, 13% by weight of microcrystalline cellulose, 10% by weight of calcium hydrogen phosphate dihydrate, 1% by weight of precipitated silica, and 1% by weight of magnesium stearate.
(c) A tablet containing 6% by weight of baclofen, 27% by weight of mannitol, 25% by weight of xanthan gum, 20% by weight of crospovidone, 20% by weight of microcrystalline cellulose, 1% by weight of precipitated silica, and 1% by weight of magnesium stearate.
(S) An antipruritic agent containing nalbuphine or a pharmaceutically acceptable salt or ester thereof.
(C) An easily swallowable tablet characterized by blending (a) one or more members selected from the group consisting of carrageenan, sodium alginate, and xanthan gum, and (b) one or more members selected from the group consisting of crospovidone, sodium carboxymethyl starch, croscarmellose sodium, and low-substituted hydroxypropyl cellulose.
(S) A tablet containing 20% by mass of iota-carrageenan, 10% by mass of crospovidone, 34.3% by mass of corn starch, 17.1% by mass of carboxymethylcellulose, 16.6% by mass of crystalline cellulose, 1.5% by mass of light anhydrous silicic acid, and 0.5% by mass of magnesium stearate.
(T) A novel pharmaceutical composition with improved release characteristics, comprising at least one active agent or a pharmaceutically acceptable salt, ester, prodrug, solvate, hydrate, or derivative thereof, and at least two swellable, pH-independent polymers, at least one of which is hydrophilic, the amount of said polymer system being less than about 80% w/w of the composition, and any other pharmaceutically acceptable excipients, which provides therapeutic concentrations of the active agent for an extended period of time.
(h) An oral care dentifrice composition comprising: a. about 1% to about 40% by weight of the composition of a retention agent selected from the group consisting of water-soluble hydrophilic gums, water-soluble hydrophilic polymers, and mixtures thereof, said retention agent having the property of hydrating upon exposure to water or saliva, thereby forming a fully hydrated mass that provides said composition with a Retention Index of about 1 to about 4; and b. a safe and effective amount of a topical oral care carrier, wherein said composition is a non-cariogenic, chewable solid unit dosage form, said composition comprising less than about 65% by weight of water-insoluble particles.
(T) A composition for oral administration containing calcium L-threonate, characterized in that it contains crystalline cellulose and guar gum and/or gelatin.
(T) A solid sustained-release pharmaceutical tablet for administration to a host, comprising a therapeutically effective amount of a pharmaceutically active ingredient and a sustained-release carrier therefor, wherein the sustained-release carrier comprises (a) xanthan gum, guar gum, and alginic acid or a pharmaceutically acceptable salt thereof, and (b) a cellulose ether, wherein the carrier is present in the formulation in an amount less than about 40% by weight of the tablet, the hydrocolloid and cellulose ether are present in synergistic amounts to delay the release of the pharmaceutically active ingredient, the hydrocolloid being present in an amount ranging from about 0.3% to 7.0% by weight of the tablet, the cellulose ether being present in an amount ranging from 3% to 20% by weight of the tablet, and the cellulose ether being present in the carrier in an amount greater than about 33% by weight of the carrier.
(g) Tablets obtained by compressing a mixture of gefenezine (600 mg) mixed with 48 mg xanthan gum and 7.5 mg silicified microcrystalline cellulose in a V-blender for 120 minutes to give a total weight of 800 mg.
(n) Tablets obtained by compressing a mixture of gefenezine (600 mg) mixed with 80 mg xanthan gum and 7.5 mg silicified microcrystalline cellulose in a V-blender for 120 minutes to give a total weight of 800 mg.
(D) A tablet having a three-layer structure, which, when measured based on the disintegration test method of the Japanese Pharmacopoeia, has a disintegration time of 10 minutes or less for the first layer, 120 minutes or more for the second layer, and 60 to 80 minutes for the third layer.
(J) A pharmaceutical or functional food drug formulation or a Chinese herbal or crude drug formulation that is dispersed in hot water or water and prepared just before use within one hour from preparation to administration, wherein the pharmaceutical or Chinese herbal or crude drug extract powder is mixed with at least one of a thickener and a gelling agent and a dispersant to be processed into any one of powder, granules, tablets, blocks, or capsules, and when prepared just before use by dispersing a single dose in 100 mL of hot water or water, the thickened liquid has a viscosity of 50 mPa·s to 500 mPa·s at 20°C measured with an E-type viscometer, and the gel has a hardness of 3×102 to 2×104 (N/m2) at 10°C to 60°C, an adhesiveness of 1.5×103 (J/m3) or less, and a cohesiveness of 0.2 to 0.9. mixing a powder of a gelling agent with a powder of crystalline cellulose;
The method for producing tablets according to claim 1, further comprising a step of compressing the obtained mixed powder into tablets without spraying a liquid thereon.