JP7390695B2 - Tablets and tablet manufacturing method - Google Patents

Description

The present invention relates to a tablet and a method for manufacturing the same.

In recent years, the market size of health foods and supplements in Japan is expected to continue to expand due to the increasing health consciousness of consumers and the introduction of a new system for food labeling, the Food with Function Claims System. Ru. Tablets are often used for oral administration among supplements, but taking large tablets or multiple tablets at the same time can be difficult for people who are not good at swallowing tablets, and especially for children and the elderly who have poor swallowing ability. It is often difficult.
In order to make tablets easier to swallow, it is necessary to improve the slipperiness of tablets and the difficulty in getting them stuck in the throat. Taking this point into consideration, several techniques have been reported to date in which coatings of solid agents such as tablets are devised (Patent Documents 1 to 3). However, even though the coating makes the tablet surface slippery and improves the ease of taking it to some extent, the resistance when passing through the complex-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 Publication No. 2014-534977

An object of the present invention is to provide a tablet that can be easily taken with little resistance even by people who are not good at taking tablets. In addition, tablets with a coating according to the prior art tend to increase in volume due to the coating layer and become large in size, and the coating is applied to the tablet surface after tabletting, which requires time and manufacturing costs. The purpose of the present invention is to prevent tablets from increasing in size and to provide tablets that are both easy to swallow and reduce manufacturing costs.

The present invention comprises a gelling agent;
The present invention provides a tablet having a bare tablet containing one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch decomposition products.

The present invention also provides a method for producing the tablet, which comprises: a gelling agent; The present invention provides a method for manufacturing a tablet having a plain tablet, which comprises tableting a raw material powder containing the above.

The tablet having a bare tablet of the present invention contains a liquid medium such as water and becomes elastic when the bare tablet part comes into contact with saliva or ingested moisture (hereinafter referred to as a liquid medium such as water), It is characterized by a slimy feeling on the surface of the tablet, making it easy to swallow. Here, the liquid medium such as water means water, tea, soft drinks, milk, other aqueous liquids commonly used for drinking, saliva, or mixtures thereof. Furthermore, in the tablet having a bare tablet of the present invention, since the entire surface of the tablet is not covered with a coating layer, manufacturing costs can be reduced and the tablet can be prevented from increasing in size. Furthermore, the tablet having a bare tablet of the present invention is excellent in disintegrating easily after ingestion.
Further, the method for producing a tablet having a bare tablet of the present invention can produce the tablet having a bare tablet of the present invention in an industrially advantageous method.

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

Hereinafter, the present invention will be explained based on its preferred embodiments.

The tablet of the present invention contains a gelling agent and one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch decomposition products. Has a bare lock. Generally, a bare tablet (also referred to as a plain tablet) refers to a tablet without a coating layer formed on its surface. As used herein, the term "tablet with a bare tablet" refers to a tablet in which there is a part on the surface of the tablet on which no coating layer is formed, and this part is in the state of a bare tablet (hereinafter referred to as "tablet with a bare tablet"). The part where no coating layer is formed is called the bare tablet part). In addition, the term "naked tablet" as used herein means a tablet on which no coating layer is substantially formed on the surface (a tablet in which the ratio of the area covered by the coating layer to the surface area of the tablet is less than 5%). do. As used herein, the term "uncoated tablet" is a concept included in "tablet with a naked tablet."

The tablet having a bare tablet of this embodiment exhibits sliminess (also referred to as slipperiness) when a liquid medium such as water comes into contact with the bare tablet portion. 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 portion refers to a portion located on the surface side of the bare tablet portion, and refers to a range of 0 mm or more and 1 mm or less from the surface of the bare tablet portion toward the center. The tablet of this embodiment has a gelling agent on the uncoated tablet portion, particularly on the outermost surface of the uncoated tablet portion, so that the surface of the uncoated tablet portion becomes slimy when it comes into contact with a liquid medium such as water. As a result, the tablet having a bare tablet of this embodiment can be easily swallowed without providing a coating layer. It is particularly preferable that the tablet having a bare tablet has a gelling agent on the entire outermost surface of the bare tablet portion. In this specification, if it can be confirmed that the gelling agent is present at two or more different locations on the outermost surface of the bare tablet, it can be said that the entire outermost surface of the bare tablet contains the gelling agent. Here, the presence of the 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 a liquid medium such as water to gel it. As described below, a tablet having a bare tablet having a gelling agent on the entire outermost surface of the bare tablet portion can be easily obtained as a tablet of a mixed powder containing a gelling agent and a specific excipient. be able to.

In the tablet having a bare tablet of the present invention, the presence of the bare tablet portion exerts the effect of the gelling agent, so it is preferable that the bare tablet portion is present on the outermost surface of the tablet. Specifically, the ratio 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, particularly preferably 95% or more. In addition, when the tablet having a bare 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 is substantially Most preferably, there is no coating layer (meaning that the proportion of the surface area of the tablet covered by the coating layer is less than 5%). Further, when the tablet having a bare tablet of the present invention has a coating layer, the thickness of the coating layer is preferably 3 mm or less, more preferably 2 mm or less, particularly preferably 1 mm or less from the surface of the bare tablet portion toward the center. By setting the thickness of the coating layer to 1 mm or less, the effect of the gelling agent can be easily exhibited, manufacturing costs can be reduced, and furthermore, it is possible to prevent the tablet from increasing in size. When the coating layer covers only a part of the tablet, the coating layer may be present continuously in one part, or may be dispersed in the form of islands or the like. For example, if a coating layer exists on a part of the tablet surface by sprinkling powder other than gelling agent (e.g. sugar or other seasoning) on the surface of the tablet, It is acceptable because the effect is achieved by the gelling agent present.

A tablet having a bare tablet may have a structure in which a surface portion and a portion closer to the center are distinguished from each other, or may not have such a structure. For example, a tablet having a plain tablet may have a multi-layer structure like a hard-coated tablet. Among these, it is preferable for the tablet having a bare tablet not to have a multi-layer structure but to have a single-layer structure in terms of ease of manufacture and the like.

1. Gelling Agent Tablets with bare tablets have a gelling agent. In the present invention, it is preferable to have a gelling agent on the outermost surface of a bare tablet, but it is also possible to have a gelling agent on a location other than the outermost surface. For example, a tablet having a bare tablet may contain a gelling agent in both the outermost surface portion and a portion closer to the center (also referred to as the center portion). An example of such a tablet having a bare tablet is a tablet having a single layer structure. In a tablet having a bare tablet, the composition of the outermost part and the composition of the center part may be the same or different, but it is preferable that the composition be the same from the viewpoint of ease of manufacturing the tablet having a bare tablet. The presence of a gelling agent in the center of a tablet having a bare tablet can be determined by, for example, cutting the tablet having a bare tablet in half with a cutter or the like, and detecting the presence of a gelling agent in a portion 1 mm ultra-center side from the surface of the tablet having a bare tablet. This can be confirmed by scraping off about 30 mg of the area with a scalpel or the like, and adding an appropriate amount of a liquid medium such as water to gel it. Note that the components listed as disintegrants described below are not included in the gelling agent in the present application.

As the gelling agent, a substance that is powdery (particulate) and exhibits sliminess when it contains a liquid medium such as water is used. Gelling agents include xanthan gum, locust bean gum, guar gum, mannan, glucomannan, hyaluronic acid, agar, alginic acid, tamarind gum, psyllium seed gum, tara gum, carrageenan, acacia gum, arabic gum, gati gum, tragacanth gum, karaya gum, and cassia gum. Natural polysaccharides such as , rhamsan gum, welan gum, macrohomopsis gum, curdlan, pullulan, gellan gum (deacylated gellan gum, native gellan gum), pectin, and soybean polysaccharides; protein decomposition products such as collagen; Amino acids; at least one selected from biopolymers such as polylactic acid and polyglutamic acid, and salts and derivatives thereof. Among these, natural polysaccharides are particularly preferred.
Examples of the derivatives include hyaluronic acid derivatives, alginic acid derivatives, and polyglutamic acid derivatives. Further, examples of the above-mentioned salts include alginates, hyaluronates, polyglutamates, and the like. 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 hyaluronate include sodium hyaluronate and potassium hyaluronate. Examples of the polyglutamate 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.

In this embodiment, the gelling agent includes locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, gum arabic, gum gati, gum tragacanth, gum karaya, gum cassia, ramsan gum, welan gum, Contains one or more types selected from macrohomopsis gum, curdlan, pullulan, gellan gum, polyamino acids, polylactic acid, and their salts and derivatives (hereinafter also referred to as specific gelling agents), which disintegrates in the body after ingestion. Containing locust bean gum is particularly preferable because it is easy to disintegrate after ingestion and exhibits both disintegrability and sliminess at a high level.

In addition, it is also preferable to combine two or more types of gelling agents from the viewpoint of achieving both disintegration and sliminess, and from the viewpoint of productivity, and combining a specific gelling agent with a gelling agent other than the specific gelling agent. It 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, etc., which are gelling agents other than the specific gelling agent. For example, by combining locust bean gum with xanthan gum or guar gum, ease of swallowing due to the slimy feeling can be effectively enhanced. Furthermore, by combining guar gum with locust bean gum, it is possible to obtain a tablet that has excellent disintegration properties in the body after ingestion.

In the tablet having a bare tablet, it is preferable that the proportion of the gelling agent is 0.01% by mass or more in order to sufficiently produce a slimy feeling when it comes into contact with a liquid medium such as water. Further, it is preferable that the proportion of the gelling agent in the tablet having a bare tablet is 70% by mass or less from the viewpoint of ease of elution of the active ingredient. From these points, in the tablet having a bare tablet, the proportion of the gelling agent 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, It is 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 bare tablet of this embodiment contains at least one kind selected from the specific gelling agents in the tablet having a bare tablet, the total mass of the specific gelling agent in the tablet having a bare tablet. The preferred range of is the same as the preferred range of the gelling agent described above. Here, the total mass of at least one selected from the specific gelling agents is the mass of the one type when the tablet having a bare tablet contains only one type selected from the specific gelling agents. If the tablet containing a bare tablet contains two or more of these, it is the total mass of them.

When the tablet having a bare 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 tablet having a bare tablet is From the viewpoint of achieving both sliminess and disintegrability, the former is preferably 10 parts by mass or more and 1000 parts by mass or less, more preferably 15 parts by mass or more and 900 parts by mass or less, per 100 parts by mass of the latter. It is particularly preferable that the amount is 20 parts by mass or more and 800 parts by mass or less.

For example, when the tablet having a bare 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 bare tablet is 100% It is more preferable that locust bean gum is 10 parts by mass or more and 1000 parts by mass or less, even more preferably 15 parts by mass or more and 900 parts by mass or less, and 20 parts by mass or more and 800 parts by mass or less. is particularly preferred.

Further, when the tablet having a bare 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 bare tablet is set to 100% by mass of guar gum in order to increase the sliminess and the content of active ingredients. It is even more preferable that locust bean gum is 10 parts by mass or more and 1000 parts by mass or less, even more preferably 15 parts by mass or more and 900 parts by mass or less, and 20 parts by mass or more and 800 parts by mass or less. is particularly preferred.

2. Specific excipients A tablet having a bare tablet may contain one or more excipients selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch decomposition products (hereinafter these are specified). (also called excipients). By combining gelling agents and these specific excipients, tablets with excellent sliminess and short disintegration times can be obtained.

As mentioned above, the tablet having a bare tablet may contain one or more selected from monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch decomposition products; It is preferable to contain a combination of two or more components belonging to different categories from the viewpoint of achieving both smoothness and sliminess. Specific examples include a combination of disaccharides and cellulose, a combination of disaccharides and reduced maltose, and a combination of disaccharides and starch. Further, it is more preferable to include 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.

Examples of sugar alcohols include monosaccharide alcohols, disaccharide alcohols, and trisaccharide alcohols and higher alcohols. Examples of monosaccharide alcohols include tetritols such as erythritol, D-threitol, and L-threitol, pentitols such as D-arabinitol and xylitol, D-iditol, galactitol (dulcitol), and D-glucitol (sorbitol). Examples include cyclitol such as hexitol and inositol, mannitol, boremitol, ribitol, perseitol, and D-erythro-D-galacto-octitol. Examples of the disaccharide alcohol include reduced maltose (maltitol), lactitol, and reduced palatinose (isomalt). Examples of alcohols having trisaccharides or higher include maltotriitol, isomaltotriitol, panitol, and the like. The sugar alcohol is preferably at least one selected from disaccharide alcohols, particularly at least one selected from reduced maltose and reduced palatinose, from the viewpoint of manufacturability such as obtaining hardness of compressed tablets. Preferably it is a seed.

Monosaccharides include glucose, galactose, fructose, and mannose. Among these, glucose is preferred from the viewpoint of easy availability and achieving both disintegration and sliminess.

Disaccharides include sucrose, maltose, lactose, 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 included, from the viewpoint of achieving both disintegrability and sliminess, it is more preferable that the disaccharide is a disaccharide other than lactose.

Examples of oligosaccharides include trisaccharides and 20saccharides, preferably trisaccharides and 10saccharides, more preferably trisaccharides and 6saccharides, and specific examples include raffinose, maltotriose, Examples include melezitose, gentianose, acarbose, stachyose, galactooligosaccharide, fructooligosaccharide, mannan oligosaccharide, isomaltooligosaccharide (isomaltotriose, panose), xylooligosaccharide, soybean oligosaccharide, nigerooligosaccharide, and milk fruct oligosaccharide. In particular, it is preferable to use isomalto-oligosaccharide or fructooligosaccharide from the viewpoint of easy availability and achieving both disintegrability and sliminess.

It is preferable for the plain tablet to contain any one of a monosaccharide, a disaccharide, and an oligosaccharide, not only from the viewpoint of taste masking but also from the viewpoint of promoting saliva secretion. In particular, it is preferable to contain these saccharides on the surface of a bare tablet.

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 refining it. For example, those corresponding to crystalline cellulose described in the Fifteenth Edition Japanese Pharmacopoeia Explanation (published by Hirokawa Shoten) can be mentioned. Crystalline cellulose can be classified into crystalline cellulose powder and crystalline cellulose composite, and any of these can be used in the tablet having a plain tablet of the present invention.

Examples of cellulose derivatives include carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and methylcellulose. Carboxymethyl cellulose is preferably one having an etherification degree of 0.2 mol/C6 to 1.0 mol/C6 from the viewpoint of easy availability and achieving both sliminess and disintegration time; More preferably, it is 8 mol/C6. Although the effects of the present invention can be obtained even when croscarmellose sodium made by internally crosslinking carboxymethyl cellulose sodium or low-substituted hydroxypropyl cellulose is included, from the viewpoint of achieving both disintegration and sliminess, cellulose derivatives More preferably, it is a cellulose derivative other than croscarmellose sodium and low-substituted hydroxypropylcellulose.

Examples of starches include natural starches. Examples of sources of starch include corn, potato, arrowroot, tapioca, canola, rice, wheat, wheat, barley, yam, and taro. When blending starch, it is particularly preferable to blend it in combination with sugar alcohol in order to achieve both disintegration and sliminess.

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, cross-linked starch, and soluble starch. Examples include starch, grafted starch, and sodium carboxymethyl starch, and pregelatinized starch is preferred in terms of both sliminess and disintegration time. When blending starch derivatives, it is particularly preferable to blend them in combination with sugar alcohols in order to achieve both disintegration and sliminess. 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, the starch derivative is a starch derivative other than sodium carboxymethyl starch. It is more preferable.

Decomposed starch products include dextrins, and those with a DE of 8 to 9.5 are preferred.

The content of the specific excipient in the tablet having a bare tablet is 10 parts by mass or more based on 100 parts by mass of the gelling agent in the tablet having a bare tablet. It is preferred that the amount of the specific excipient is 3000 parts by mass or less with respect to 100 parts by mass of the gelling agent in the tablet having a plain tablet, in order to further enhance the effect of using it in combination with the tablet. It is preferable from the viewpoint of increasing the content of active ingredients. From these points, it is preferable that the amount of the specific excipient in the tablet having a bare tablet is 10 parts by mass or more and not more than 3000 parts by mass, with respect to 100 parts by mass of the gelling agent in the tablet having a bare tablet. It is 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.

Further, 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 is also preferably 3 parts by mass or more and 70 parts by mass or less. In particular, from the viewpoint of disintegration, the specific excipient preferably accounts for 40% by mass or more, more preferably 50% by mass or more, and 60% by mass or more in the tablet having a bare tablet. is more preferable, and may be 70% by mass or more. Further, the upper limit of the amount of the specific excipient is preferably 95% by mass or less in the tablet having a plain tablet, from the viewpoint of containing the gelling agent, and more preferably 90% by mass or less.

The tablet having a bare tablet according to the present invention contains, among specific excipients, one or more selected from monosaccharides, disaccharides, oligosaccharides, starch derivatives (especially pregelatinized starch), and starch decomposition products. It is preferable to have high sliminess, and it is more preferable to contain a monosaccharide, a disaccharide, an oligosaccharide, or a starch decomposition product.

In addition, tablets in the form of bare tablets may contain specific excipients such as monosaccharides, disaccharides, oligosaccharides, sugar alcohols, crystalline cellulose, or cellulose derivatives (especially carboxymethyl cellulose), which may cause disintegration in addition to sliminess. It is preferable from the viewpoint of excellent properties, and it is more preferable to contain monosaccharides, disaccharides, oligosaccharides, sugar alcohols, or carboxymethylcellulose.
In addition, the inclusion of sugar alcohols and disaccharides improves the cohesiveness of the raw material powder for tablets, increases the hardness of compressed tablets, and improves the ease of formulation, as well as the effect of masking the unpleasant taste of active ingredients. It is also preferable in that it can be obtained.

Monosaccharides, disaccharides, oligosaccharides, sugar alcohols, crystalline cellulose, and carboxymethyl cellulose are contained as main components in a specific excipient, specifically, components accounting for 50% by mass or more in a specific excipient. Most preferably.

In addition, tablets having a bare tablet may contain a combination of a disaccharide and one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch, and starch decomposition products as specific excipients to improve disintegration. Preferred from the viewpoint of improving sliminess, and particularly preferred is a combination of a disaccharide and an oligosaccharide or a cellulose derivative. When a tablet having a bare tablet contains a combination of a disaccharide and another specific excipient as a specific excipient, from the viewpoint of achieving both sliminess and disintegration, 100 parts by mass of the disaccharide. In contrast, the amount of other specific excipients is preferably 1 part by mass or more and 1000 parts by mass or less, even more preferably 5 parts by mass or more and 300 parts by mass or less, and 5 parts by mass or more and 100 parts by mass or less. It is particularly preferable that

Moreover, it is preferable that the tablet having a bare tablet contains a combination of a sugar alcohol and starch or pregelatinized starch as a specific excipient from the viewpoint of improving disintegration and sliminess. When a tablet having a bare tablet contains a combination of sugar alcohol and starch or pregelatinized starch as a specific excipient, from the viewpoint of achieving both sliminess and disintegration, the amount of sugar alcohol per 100 parts by mass of sugar alcohol is The content of starch or pregelatinized starch is preferably 10 parts by mass or more and 1000 parts by mass or less, further preferably 30 parts by mass or more and 700 parts by mass or less, and more preferably 50 parts by mass or more and 500 parts by mass or less. Particularly preferred.

In this embodiment, starch, a starch derivative, or a starch decomposition product is contained, and combining this with xanthan gum, locust bean gum, guar gum, and salts and derivatives thereof, especially locust bean gum may also be used to achieve a balance between hardness and gelation degree. This method is preferable because it is easier to obtain a tablet having a plain tablet that is easy to swallow.
Furthermore, as described below, sugar alcohols are added to xanthan gum, locust bean gum, guar gum, and their salts and derivatives under conditions in which the surface is coated with a gelling agent and does not contain particles containing the gelling agent. It is also preferable to combine with at least one selected from the following, since it is easier to obtain tablets that have excellent hardness, ease of swallowing, and slipperiness, and are easy to swallow. Further, as described later, under the condition that a gelling agent coating layer is not included, a gelling agent composed of starch and at least one selected from xanthan gum, locust bean gum, or guar gum, and salts and derivatives thereof. It is also preferable that the tablet be a bare tablet containing reduced maltose.

A tablet having a bare tablet preferably contains a specific excipient on the outermost surface of the bare tablet portion, and further preferably contains a specific excipient in the center as well.

3. Other Ingredients It is preferable that the tablet having a bare tablet contains silicon dioxide or the like as a fluidity improving agent. Examples of silicon dioxide include fine silicon dioxide and light silicic anhydride. When containing silicon dioxide, 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. It is 8 parts by mass or less, 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.

It is preferable for the tablet having a bare tablet to contain a lubricant from the viewpoint of improving manufacturability (preventing punching during tableting). Examples of lubricants include magnesium stearate and calcium stearate. When containing a lubricant, its proportion is preferably 0.1% by mass or more and 20% by mass or less, more preferably 0.5% by mass or more and 10% by mass or less in the bare tablet of the present invention. preferable.

The tablet having a bare 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, a processed product derived from a plant, an animal, a microorganism, or the like. In addition to the above-mentioned active ingredients, specific excipients, silicon dioxide, disintegrants, lubricants, and saccharides, the tablets in the form of a bare tablet may contain binders, seasonings other than saccharides, emulsifiers, fragrances, and the like. Moreover, the tablet used in this embodiment is for oral use, that is, for internal use, and is a tablet for swallowing. It goes without saying that the tablet of this embodiment may be used as a supplement, health food, nutritionally functional food, food with functional claims, food for specified health uses, and medicine.

The tablet having a bare tablet of this embodiment contains seasonings and/or fragrances other than sugars on the outermost surface of the bare tablet part, so that saliva secretion is induced when the tablet having a bare tablet is placed in the oral cavity. can be promoted and the supply of liquid medium such as water to the tablet can be increased. As the seasoning, sweeteners, acidulants, etc. can be used. As the sweetener, sucrose derivatives of sucralose, peptide sweeteners such as aspartame, alitame, neotame, glycyrrhizin, stevia, licorice, etc. can be used. As the acidulant, organic acids can be used, examples of which include citric acid, malic acid, tartaric acid, and the like. As the fragrance, citrus flavors such as grapefruit flavor, lemon flavor, and orange flavor, as well as fruit flavors, etc. can be used.

The tablet having a bare tablet according to this embodiment may contain a disintegrant. Examples of disintegrants include baking soda (sodium hydrogen carbonate), magnesium carbonate, carmellose calcium, sodium starch glycolate, etc., which can be used as food additives, crospovidone, sodium carboxymethyl starch, croscarmellose sodium, Examples include substituted hydroxypropyl cellulose. Although the effect of the present invention is exhibited even when a disintegrant is included, from the viewpoint of excellent sliminess, it is preferable that the content of the disintegrant be small. Specifically, 100 parts by weight of a tablet having a bare tablet On the other hand, the blending amount of the 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 1 part by weight or less. Preferably, it is most preferably free.

Among the disintegrants, from the viewpoint of excellent sliminess, one or more disintegrants selected from crospovidone, sodium carboxymethyl starch, croscarmellose sodium, or low-substituted hydroxypropylcellulose (hereinafter these are referred to as specific disintegrants) It is preferable that the content of the agent (also referred to as an agent) be as small as possible. Specifically, the amount of the 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, and 3 parts by weight for 100 parts by weight of a tablet having a bare tablet. It is even more preferable that the amount is less than 1 part by weight, extremely preferably less than 1 part by weight, and most preferably that it is not contained. Note that low-substituted hydroxypropyl cellulose is produced by reacting propylene oxide and alkali cellulose at high temperatures, and when dried at 105°C for 1 hour, the hydroxypropyl cellulose contains 5.0 to 16.0% of hydroxypropyl groups. It means something that includes.

The tablet having a bare tablet according to this embodiment may contain particles containing a sugar alcohol and a gelling agent whose surfaces are coated with a gelling agent. Although the effects of the present invention are exhibited even when the surface is coated with a gelling agent and contains particles containing a sugar alcohol and a gelling agent, from the viewpoint of excellent disintegration properties, particles whose surface is coated with a gelling agent The content of the particles containing the sugar alcohol and the gelling agent is preferably small, and the content of the particles containing the sugar alcohol and the gelling agent whose surface is coated with the gelling agent is mixed with 100 parts by weight of a plain tablet. The amount 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 no content. Particles containing a sugar alcohol and a gelling agent whose surfaces are coated with a gelling agent are formed by, for example, spraying a gelling agent onto particles containing a sugar alcohol. In the present invention, the tablet having a bare tablet does not contain sugar alcohol whose surface is coated with a gelling agent and particles containing the gelling agent, and the gelling agent and the specific excipient are uniformly mixed. By keeping it in a stable state, it becomes easier to shorten the disintegration time.

The fact that the surface is free of sugar alcohols and gelling agent-containing particles coated with a gelling agent can be confirmed by, for example, examining the distribution of the gelling agent in a bare tablet using cross-sectional imaging such as TOF-SIMS. You can check this by At this time, if a layer in which the gelling agent is locally concentrated is not observed and the gelling agent is uniformly dispersed in the bare tablet, the tablet having the bare tablet of the present invention has a surface It can be said that it does not contain sugar alcohol coated with a gelling agent and particles containing the gelling agent.

4. Physical properties etc. Considering the ease of swallowing of a tablet having a bare tablet, for example, in the case of a disk-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 150 mg or more. Most preferably 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 bare tablet of the present invention, the maximum value of stress (maximum stress) generated when the tablet moves in a silicone tube can be measured by the method described below. Specifically, the tablet was placed on a plastic substrate, 0.2 μL of 25°C water was dropped with a dropper per 1 mm ² of surface area of the tablet, and after being held in that state for 10 to 20 seconds, the following It can be measured according to the procedure. In the tablet having a bare tablet of the present invention, the maximum stress is preferably less than 20N, more preferably 15N or less, even more preferably 10N or less, and particularly preferably 5N 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 FIG. 1, numeral 1 is a tablet, numeral 2 is a slit, and numeral 3 is a silicon tube.

<Maximum stress measurement procedure>
A silicone tube arranged along the vertical direction and fixed so as to be movable in the vertical direction, and a pair of slits fixed with the silicone tube sandwiched in the horizontal direction are used, and the bottom of the slit in the silicone tube is One tablet is filled in the side, and the maximum stress is measured when the silicone tube is moved 20 mm upwardly relative to the tablet along the slit at a speed of 0.5 mm/sec. The silicone tube used in the measurement is one whose cross-sectional area is smaller than the cross-sectional area of the tablet and larger than 40% of the cross-sectional area of the tablet. The ratio of the cross-sectional area of the tablet to the cross-sectional area of the silicone tube is preferably 40% or more and 60% or less, more preferably 45% or more and 55% or less.

The above-mentioned vertical direction is a direction perpendicular to a horizontal plane. Moreover, the above-mentioned horizontal direction refers to a direction perpendicular to the vertical 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 taken in a direction orthogonal to the longitudinal direction of the silicone tube in a state where no tablets are filled.
Further, the cross-sectional area of the tablet refers to the area of the cross-section having the largest area among the cross-sections of the tablet filled in the silicone tube, taken along a plane perpendicular to the longitudinal direction of the silicone tube.

Moreover, the tablet having a bare tablet of this embodiment has a disintegration time using water as a solvent 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 in view of ease of manufacturing tablets. Disintegration time means the time it takes for a sample in a solvent to disintegrate. The procedure for measuring the disintegration time follows the method described in item "6.09" "Disintegration test method" in the 15th edition of the Japanese Pharmacopoeia. When using a tablet with a diameter of 3 to 15 mm, a tablet 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 number: NT-400. The tablet of this embodiment preferably has a disintegration time of 0.01 minutes/mm or more and 25 minutes/mm or less, more preferably 0.05 minutes/mm or more and 20 minutes/mm or less, based on the tablet thickness. It is 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 0.2 min/mm or more and 4 min/mm or less. The following is most preferable.

<Procedure for measuring disintegration time>
One tablet is placed in each of the six glass tubes of a disintegration tester. Each glass tube has an open upper and lower surface, and a stainless steel mesh with a mesh opening of 1.8 mm to 2.2 mm is attached to the lower surface of the glass tube. The glass tube containing the tablet is placed in water at 37±2°C and the disintegration tester is activated. Observe the glass tube in the disintegration tester, and when it is confirmed that the tablet is about to disintegrate, pull up the glass tube and observe the disintegration of the tablet. Repeat this process and observe until the tablet is completely disintegrated. The time from when the disintegration tester is activated to when all six tablets disintegrate is measured, and the measured time is defined as the disintegration time. The tablet is considered to have disintegrated if no tablet residue is found in the glass tube, or if it is a soft substance that does not retain its original shape.

5. Manufacturing method Hereinafter, a preferred method for manufacturing the tablet having a bare tablet of the present embodiment will be further described.
The production method of this embodiment includes a gelling agent, one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch decomposition products (specific excipients). ) is used to tablet raw material powder containing
The gelling agent, sugar alcohol, monosaccharide, disaccharide, oligosaccharide, cellulose, cellulose derivative, starch, starch derivative, and starch decomposition product include those mentioned above. In powders containing gelling agents and specific excipients, ingredients other than the gelling agent and specific excipients include the excipients, disintegrants, binders, lubricants, emulsifiers, and active ingredients listed above. Examples include ingredients, seasonings, fragrances, etc. The preferred range of the mass ratio of the gelling agent in the raw material powder, the preferred mass ratio of the preferred gelling agent component, the preferred mass ratio of a specific excipient, and the preferred mass ratio of the excipient, disintegrant, and lubricant. is the same as the preferred mass ratio in the plain tablet described above.

Furthermore, as mentioned above, the naked tablet may be a cored tablet or a coreless tablet. In the case of a cored tablet, a raw material powder containing any core may be used as the raw material powder. be locked.

The raw material powder containing a gelling agent and a specific excipient may be a mixture itself of a powdered gelling agent, a powdered specific excipient, and other powdered components included as necessary. Alternatively, it may be a granulated powder obtained by granulating a mixture of a powdered gelling agent, a powdered specific excipient, and optionally powdered other components.
As the granulation method, any known granulation method used when manufacturing oral tablets by a granule compression method can be used without particular limitation.

The method for producing a tablet having a bare tablet of the present invention preferably includes a powder of a gelling agent, a sugar alcohol, a monosaccharide, a disaccharide, an oligosaccharide, a cellulose, a cellulose derivative, a starch, a starch derivative, and a starch decomposition product. and a step of tableting the obtained mixed powder without spraying an aqueous solution in which a gelling agent is dissolved. As mentioned above, this is because the gelling agent is uniformly coated with a specific excipient, compared to a bare tablet obtained by compressing particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent. This is because the plain tablets mixed with the above are superior in terms of disintegration and sliminess, especially in terms of disintegration.

As mentioned above, the tablet having a bare tablet of the present embodiment is a tablet of a mixed powder containing a gelling agent and a specific excipient, particularly the tablet obtained without spraying an aqueous solution containing a gelling agent. It is preferable to use a tablet obtained by compressing a mixed powder because it is possible to easily obtain a bare tablet in which the gelling agent is present on the entire surface of the tablet. "Tablets of mixed powder containing gelling agent and specific excipient" and "Compressed powder mixture (containing gelling agent and specific excipient) obtained without spraying an aqueous solution containing gelling agent" Even if the manufacturing method is included in the expression "tablets obtained by compressing the mixed powder into tablets," the presence form of gelling agents and specific excipients in the bare tablets is not explained in this specification. It would be impractical to specify it in more detail, and there were impossible circumstances that forced us to use this expression.

The tablet having a bare tablet of this embodiment has the same hard properties as a tablet having a bare tablet that does not contain a gelling agent during storage because the bare tablet contains a gelling agent as described above. Upon contact with a liquid medium such as water when ingested, 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 uncoated tablet portion is maintained, and the active ingredients present in the uncoated tablet portion are prevented from dissolving in the oral cavity. As described above, the tablet of the present embodiment has the characteristic that it swells with a liquid medium such as water and produces a slimy feeling 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;
Tablets with a bare tablet containing one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch decomposition products (sprayed with an aqueous solution containing a gelling agent) (excluding tablets obtained by compressing particles granulated by

a gelling agent;
Tablets with a bare tablet containing one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch decomposition products (crospovidone, sodium carboxymethyl starch, (excluding those containing carmellose sodium or low-substituted hydroxypropylcellulose).

a gelling agent;
A tablet having a bare tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starches, and starch decomposition products.

Locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, gum arabic, gati gum, tragacanth gum, karaya gum, cassia gum, ramsan gum, welan gum, macrohomopsis gum, curdlan, pullulan, gellan gum , polyamino acids, polylactic acid, and one or more selected from salts and derivatives thereof;
A tablet having a bare tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starches, and starch decomposition products.

Locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, gum arabic, gati gum, tragacanth gum, karaya gum, cassia gum, ramsan gum, welan gum, macrohomopsis gum, curdlan, pullulan, gellan gum , polyamino acids, polylactic acid, and one or more selected from salts and derivatives thereof;
One or more selected from xanthan gum, guar gum, alginic acid, and carrageenan,
A tablet having a bare tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starches, and starch decomposition products.

a gelling agent;
Disaccharide and
A tablet having a bare tablet containing one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starches, and starch decomposition products.

a gelling agent;
sugar alcohol and
and one or more selected from starch and pregelatinized starch,
A tablet having a bare tablet that does not contain a coating layer of a gelling agent.

Hereinafter, the present invention will be explained in more detail with reference to Examples. However, the scope of the present invention is not limited to such embodiments. Note that commercially available products were used as the materials listed in Tables 1-3. In particular, Isomalto 900P manufactured by Showa Sangyo Co., Ltd. was used as the isomaltooligosaccharide. Further, as the crystalline cellulose, KC Flock W-400G manufactured by Nippon Paper Industries Co., Ltd. was used. As carboxymethylcellulose, carboxymethylcellulose calcium having a degree of etherification of 0.5 to 0.7 mol/C6 was used. Perfiller 102 manufactured by Freund Sangyo Co., Ltd. was used as the starch powder. As the pregelatinized starch, NON-GMO Corn Alpha-Y manufactured by Sanwa Starch Industries Co., Ltd. was used. As the dextrin, Max 1000 manufactured by Matsutani Chemical Industry Co., Ltd. was used.

1. Evaluation of sliminess [Example 1]
As a raw material powder, 400 grains of various raw materials (excluding calcium stearate) were mixed in a plastic bag according to the blending ratio shown in Table 1, and then passed through a sieve, and further 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 bare tablet was measured using a Schleuniger tablet hardness meter. In addition, when the lock diameter (diameter) and lock thickness of the obtained bare tablet were measured using a digital caliper (Digimatic Caliper CD-15AX; Mitutoyo), the hardness was 7.4 kgf, the lock diameter was 10 mm, and the lock thickness was 3.52 mm. Ta. Moreover, when the weight of one of the obtained bare tablets was measured, it was 270 mg. Note that the hardness, tablet diameter, tablet thickness, and weight are the average values of the measured values for each of the three tablets.

[Example 2]
Bare tablets were obtained in the same manner as in Example 1, except that the blending ratio of the raw material powder was changed according to the blending ratio in Table 1. When the obtained bare tablet was measured in the same manner as in Example 1, 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]
Regarding the bare tablets obtained in Examples 1 and 2, throat myoelectric potential measurements and questionnaires regarding the feeling of taking were conducted in a single-blind crossover manner.
In addition, in order to evaluate the slipperiness of the tablets, the time taken to slide down the slope was measured.

・How to take bare tablets Six healthy adults who were aware that they were not good at taking tablets were selected as subjects (male/female ratio 2:4). The administration method was to first put 4 target tablets in the mouth, then 20 mL of 22°C water in the mouth, and then take the tablets with water.

- Myoelectric potential measurement Myoelectric potential measurement was performed using an electromyometer (wireless myoelectric measurement/analysis system "Lateo" manufactured by AM Science Co., Ltd.). The measurement method followed the manual attached to the electromyograph, and specifically, it was performed as follows. Electromyography electrodes were attached to the throat, and the subjects were made to drink 20 mL of water, the same amount as when taking the bare tablet, in order to acclimatize the throat. Next, the myoelectric potential of the throat was measured when 20 mL of water was taken. Thereafter, the myoelectric potential in the throat was measured for each test group when the four tablets were placed in the mouth and taken with 20 mL of water. The amount of muscle activity was determined from the integral value calculated based on the obtained myoelectric potential (unit: volt (V)), and the relative value was calculated when the amount of muscle activity when only water was taken was taken as 100 (%). . The relative value of one exercise per person was added up and divided by the number of people, which was defined as the amount of muscle activity (%). Note that in FIGS. 1 to 3, 1 count is 1/200 second.
The measurements in each test group were performed after a rest period of about 5 minutes, and the order in which the naked tablets were taken was changed for each subject.

・Survey The lowest rating (-3 points) for slipperiness is when the tablet does not get stuck and does not go down the throat, making it difficult to swallow. The drink was evaluated on a 7-point scale, with the highest rating (3 points) being that it was slippery and easy to drink without getting stuck.
For stickiness, the lowest rating (-3 points) is when the product is so sticky that it feels like it sticks to the tongue or pharynx, making it difficult to swallow. They were evaluated on a 7-point scale with the highest rating being 3 points.

- Slope sliding time Water was supplied at a rate of 150 ml per minute from the top of the channel to an aluminum channel with a U-shaped cross section (straight in side view, channel length 90 cm, width 1.2 cm) that was fixed at an angle of 30 degrees. In this state, one bare tablet was slid from a position 10 cm below the upper end of the channel, and the time (seconds) required for it to slide 80 cm to the lower end was measured. The test was conducted 5 times, and the average value of the 5 times was calculated and used as the slope sliding time (seconds).

The amount of throat muscle activity (%) obtained by myoelectric potential measurement is shown in Table 1, and typical electromyograms are shown in FIGS. 2 to 4.
Table 1 shows the average values of the six participants and the measurement results of slope sliding time (seconds) regarding the evaluation scores obtained through the questionnaire. In Table 1, the unit of composition of the naked tablet is parts by mass.

As is clear from Table 1 and Figures 2 to 4, the naked 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. It is a bare tablet that is easy to swallow, requiring no force when taking it, and making swallowing less stressful. The questionnaire also shows that although the tablets feel slippery, they do not stick to the tongue or pharynx and are easy to swallow.
In addition, the slipperiness and stickiness of the plain tablet containing crospovidone, sodium carboxymethyl starch, croscarmellose sodium, or low-substituted hydroxypropyl cellulose are lower than those of Example 1 or 2.

In addition, when comparing the slope sliding time, as shown in Table 1, Examples 1 and 2 slide down in less than 2 seconds, and the bare tablet of Example becomes slippery when it comes into contact with water, making it easier to swallow. You can see that it has become a thing.
Note that the plain tablet containing crospovidone, sodium carboxymethyl starch, croscarmellose sodium, or low-substituted hydroxypropylcellulose has lower slope sliding properties than Example 1 or 2.

From the above, in the case of bare tablets containing a gelling agent and specific excipients (sugar alcohol, pregelatinized starch), even people who are not good at taking tablets can easily take them with little resistance. Ta.

2. Evaluation of disintegration [Examples 3 to 6]
According to the compounding ratio in Table 1 below, the hardness was 9 kgf, the tablet diameter was 9 mm, and the tablet thickness was 4.81 to 5.08 mm (Example 3 was 4.81 mm, Examples 4 and 6 were 4.89 mm, Example 5 was 5. Bare tablets were obtained in the same manner as in Example 1, except that the tablet size was changed to 0.08 mm) and the weight was changed to 300 mg.
The disintegration time of the obtained naked tablets was measured by the method described below. The results are shown in Table 2.

・Disintegration time: Using a disintegration tester (Toyama Sangyo Co., Ltd., model number: NT-40H), n = 6, the disintegration time was measured. Note that water was used as the solution.

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

As is clear from Table 2, it was found that the plain tablet 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 blended, the disintegration time was only about 20% shorter than when it was not blended.

3. Evaluation of sliminess and disintegration time [Examples 7 to 14, 16 to 21, Comparative Example 1]
Bare tablets were obtained in the same manner as in Example 1 according to the blending ratio in Table 3 below. The obtained bare tablets of Examples 7 to 14, 16 to 21, and Comparative Example 1 had the same hardness, tablet diameter, and tablet thickness as 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 charged into a fluidized bed granulator (fluidized bed granulation drying/coating machine model: FD-LAB-1 model, Powrex) to form a suspension of crystalline cellulose. After spraying, granulation is performed by spraying a suspension of xanthan gum diluted with hot water to a concentration of 0.1% (w/v), and a coating layer of xanthan gum is formed on the surface of the particles consisting of a mixed powder of sorbitol and maltose. A formed particle composition (particles containing a sugar alcohol and a gelling agent whose surfaces were coated with a gelling agent) was obtained.
After mixing 0.5 parts by mass of calcium stearate into the obtained particle composition, it was tableted using a rotary tabletting machine (Kikusui Seisakusho), and the hardness, tablet diameter, and tablet thickness were the same as in Examples 3 to 5. A bare tablet weighing 300 mg was obtained. The amounts of crystalline cellulose and xanthan gum in the bare tablets were as shown in Table 1.

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

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

<Maximum stress measurement procedure>
The bare tablet was placed on a plastic substrate, and 0.2 μL of 25°C water was dropped with a dropper per 1 mm ² of surface area of the bare tablet, and the tablet was held in that state for 15 seconds.
A silicon tube with an inner diameter of 9 mm and an outer diameter of 11 mm is arranged along the vertical direction so that the longitudinal direction matches the vertical direction and is fixed so as to be movable in the vertical direction, and the silicon tube is fixed with the silicon tube sandwiched in the left and right direction. Using the pair of slits prepared above, one of the above-mentioned bare tablets (tablet diameter: 9 mm) was filled into the lower side of the slit in the silicone tube. The maximum stress when the silicone tube is moved 20 mm upwards against the bare tablet at a speed of 0.5 mm/sec along the slit is measured using a creep meter (RE2-33005C) manufactured by Yamaden Co., Ltd. did. The cross-sectional area of the silicone tube used in the measurement was 50% of the cross-sectional area of the bare tablet. If the stress exceeded 20, the measurement was terminated at that point. As the silicone tube, a clear silicone square tube manufactured by Fuso Rubber Sangyo Co., Ltd. was used. A special cylindrical extrusion jig (AT-43446) manufactured by Yamaden Co., Ltd. was used as the slit, and this was fixed at a position where the minimum distance between them was 2 mm.
The maximum stress was determined as the average value of three series.

The units in 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, compared to the plain tablet of Comparative Example 1 which contained only specific excipients and no gelling agent, gelling agent and specific The maximum stress of the bare tablets of Examples 7 to 21 containing excipients is significantly reduced.
Moreover, the results of Examples 7 to 14 show that, among specific excipients, the maximum stress is particularly low in the case of a bare tablet containing a monosaccharide, a disaccharide, an oligosaccharide, or a starch decomposition product.

Furthermore, from the comparison of Examples 15 and 16, it was found that the sugar alcohol was not used as the gelling agent compared to the plain tablet obtained by compressing the particles containing the sugar alcohol and the gelling agent whose surfaces were coated with the gelling agent. It can be seen that the mixed and compressed plain tablets have a shorter disintegration time and a lower maximum stress.

In addition, compared to a plain tablet obtained by compressing particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent, a plain tablet obtained by mixing a sugar alcohol with a gelling agent and compressing it is more The tendency for the collapse time to become shorter and the maximum stress to become lower is observed not only when sorbitol is used as the sugar alcohol, but also for sugar alcohols other than sorbitol (such as erythritol and mannitol).

In addition, from the results of Examples 17 to 21, when locust bean gum is used as a gelling agent, the disintegration time is particularly shortened and the maximum stress is lowered. It can be seen that locust bean gum is particularly excellent among gelling agents.

In the same manner as in Example 1, the following plain tablets (Formulation Examples 1 to 41) were produced. All of the bare tablets had excellent sliminess and disintegration properties. In particular, we will focus on bare tablets containing a combination of two or more gelling agents, bare tablets containing one or more selected from monosaccharides, disaccharides, oligosaccharides, starch derivatives, and starch decomposition products, and those containing specific excipients. Bare tablets containing a combination of two or more components belonging to different categories, and coated tablets containing a combination of disaccharides and one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch and starch decomposition products, are excellent. It had excellent sliminess and disintegration properties. In addition, the bare tablets prepared in Formulation Examples 1 to 41 were sprinkled with sucrose and adjusted so that the proportion of the surface area of the tablet covered by the coating layer was 20% or more and less than 30% (sucrose was sprinkled with water). Tablets with bare tablets prepared by adjusting the coating ratio by adhesion also had excellent sliminess and disintegration properties. Similarly, bare tablets prepared in such a way that the proportion of the surface area of the tablet covered by the coating layer was 5% or more and less than 10% were also excellent in sliminess and disintegration.

1 tablet 2 slit 3 silicone tube

The tablet having a bare tablet of the present invention is easy to swallow, and there is no need to coat the entire surface, so it is possible to avoid increasing the size due to coating, and the manufacturing cost can be reduced by not coating. can. It also has excellent disintegration after ingestion. Therefore, it is clear that the tablet having a bare tablet of the present invention can be used or manufactured as a supplement, health food, nutritionally functional food, food with functional claims, food for specified health uses, pharmaceuticals, etc., and is useful. be.

Claims (3)

At least one selected from locust bean gum and guar gum ;
Tablets with a bare tablet containing one or more selected from sugar alcohols and dextrins (However, the following (a), (b), (f), (ke), (k), (sa), ( (a) and (h) are excluded.
(A) The following components (a), (b), (c) and (d):
(a) an agent with therapeutic activity;
(b) A gelling agent consisting of a heteropolysaccharide gum and a homopolysaccharide gum that can crosslink 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: The gelling agent which is 1;
(c) an inert diluent selected from the group consisting of pharmaceutically acceptable sugars, polyhydric alcohols, industrially produced direct compression diluents, and mixtures thereof; and (d) a drug. Contains a scientifically acceptable hydrophobic substance,
The ratio of the inert diluent (c) to the gelling agent (b) is 1:8 to 8:1,
controlled-release solid dosage forms of oral medicines used to treat diseases in patients suffering from them.
(a) 15 to 40% by mass of at least one polysaccharide thickener selected from the group consisting of xanthan gum, carrageenan, and guar gum, 15 to 40% by mass of agar for disintegration, 10 to 70% by mass of water-soluble saccharides, and A tablet-shaped thickener containing 0.2 to 10% by mass of metal salts and having a hardness of 15 to 70N.
(F) Contains 15-45% by mass of polysaccharide thickener, 15-40% by mass of cellulose, 5-70% by mass of water-soluble saccharide, and 0.2-10% by mass of metal salt, and has a hardness of 15-70N. Tablets that are.
(k) In weight% based on the final tablet weight,
(a) Cephadroxil monohydrate 50%;
(b) 10-12% mixture containing 87 parts by weight of microcrystalline cellulose and 13 parts by weight of guar gum;
(c) Crosslinked polyvinylpyrrolidone 9.5-29%;
(d) Colloidal silicon dioxide 2.5-10%;
(e) dibasic calcium phosphate 4-19%; and (f) uncoated tablets of cefadroxil monohydrate obtained by direct compression of an anhydrous pharmaceutical composition consisting of 9-21% mannitol or maltitol. A tablet which can be orally administered to humans by swallowing, chewing or disintegrating with water to form a drinkable suspension.
(co) A sustained release oral preparation comprising torsemide or a pharmaceutically acceptable salt thereof and a sustained release excipient.
(S) A tablet formed by compressing a particle composition containing a sugar alcohol and a water-insoluble polymer.
(t) Contains (a) an active agent; (b) a thickener; and (c) a carbohydrate agent, wherein the ratio of the (b) thickener to the (c) carbohydrate agent is 1:7 or more. It is a solid drug that turns into a paste when it comes into contact with saliva.
(h) A particle composition for an easy-to-take solid preparation containing a sugar alcohol and a gelling agent that exhibits slipperiness upon contact with water, wherein a part or the entire surface of the particle composition comprises the gelling agent. A tablet obtained by compressing the above particle composition, characterized in that the particle composition is coated with: The tablet according to claim 1, which is used by directly swallowing. According to claim 1 or 2, the raw material powder containing at least one selected from locust bean gum and guar gum and one or more selected from sugar alcohol and dextrin is compressed into tablets without being sprayed with an aqueous gelling agent solution. Method for manufacturing the tablets described.