JP7096593B2 - Solid product - Google Patents

Description

The present invention relates to a solid preparation.

With the growing health consciousness of consumers in recent years and the introduction of the functional food labeling system as a new food labeling system, the size of the Japanese health food and supplement market is expected to continue to expand. To. Among supplements, solid preparations such as tablets are often used as oral preparations, but taking large tablets or multiple tablets at the same time is difficult for people who are not good at taking tablets, especially for those with low swallowing function. It is often difficult for children and the elderly.
In order to make the tablet easy to swallow, it is required to improve the slipperiness of the tablet, the difficulty of getting caught in the throat, and the like. In consideration of this point, a plurality of techniques for devising the coating of solid preparations such as tablets have been reported so far (Patent Documents 1 to 3). However, even if the coating makes the tablet surface slippery and improves the ingestibility to some extent, the resistance when passing through the pharynx having a complicated shape is still large, and the swallowing improving effect is not sufficient.

Japanese Unexamined Patent Publication No. 11-60472 US2010 / 02666787A1 US2014 / 0294598A1

An object of the present invention is to provide a solid preparation that can be easily taken by a person who is not good at drinking the solid preparation with less resistance.

The present invention is a solid preparation to be ingested orally.
The present invention provides a solid preparation which is made to increase the lubricity of the surface by contact with an aqueous liquid.

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

Hereinafter, the present invention will be described based on the preferred embodiment thereof.
The solid preparation of the present embodiment is a solid preparation to be orally ingested, and the surface lubricity is increased by contact with an aqueous liquid. The aqueous liquid referred to here refers to a liquid used for normal drinking such as water, tea, soft drinks, milk, saliva, or a mixture thereof. Since the solid preparation of the present invention contains a gelling agent, the lubricity of the surface is increased by contact with the aqueous liquid. It is preferable that the solid preparation contains a gelling agent on the surface thereof. In the solid preparation of the present embodiment, the gelling agent is not gelled in the state before administration, and the gelling agent is gelled by touching the aqueous liquid at the time of administration. As the gelling agent, a substance that is powdery (particulate) and exhibits slimy properties when it contains an aqueous liquid is used. In the present specification, gelation does not require that the presence of the gel can be confirmed, and it is sufficient that the gelling agent exhibits sliminess by coming into contact with the aqueous liquid. However, it is preferable that the presence of the gel can be actually confirmed by contact with the aqueous liquid. Specifically, the solid product is allowed to stand on a plastic substrate, 0.2 μL of water at 25 ° C. is dropped with a dropper per 1 mm ² of the surface area of the solid product, and the solid product is held in that state for 10 to 20 seconds. It is preferable to be able to confirm the presence of the gel.

When the gelling agent comes into contact with the aqueous liquid, the slimy property is exhibited because the solid preparation of the present embodiment has the maximum stress after the solid preparation is put into water, and the solid preparation is put into water. It can be confirmed by the fact that it is lower than the previous maximum stress. Here, when it is put into water, the solid preparation is allowed to stand on a plastic substrate, 0.2 μL of water at 25 ° C. is dropped with a dropper per 1 mm ² of the surface area of the solid preparation, and the state is in that state for 10 to 20 seconds. Means to hold. The procedure for measuring the maximum stress is as follows. A schematic diagram of the measuring device is shown in FIG. In FIG. 1, reference numeral 1 is a solid preparation, reference numeral 2 is a slit, and reference numeral 3 is a silicon tube.

<Measurement procedure of maximum stress>
Using a silicon 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 silicon tube sandwiched in the left-right direction, under the slit in the silicon tube. When one tablet of the solid preparation is filled on the side and the silicon tube is moved upward along the slit to move the silicon tube upward by 20 mm at a speed of 0.5 mm / sec with respect to the solid preparation. Measure the maximum stress of. As the silicon tube used for the measurement, a silicon tube having a cross-sectional area smaller than that of the solid preparation and larger than 40% of the cross-sectional area of the solid preparation is used. The ratio of the cross-sectional area of the solid preparation to the cross-sectional area of the silicon tube is preferably 40% or more and 60% or less, and more preferably 45% or more and 55% or less.

Further, in the solid preparation of the present invention, the maximum stress after putting the solid preparation measured by the above procedure into water is preferably less than 20N, more preferably 15N or less, and more preferably 10N or less. It is more preferably 5N or less, and particularly preferably 5N or less.

The above-mentioned vertical direction is a direction orthogonal to a horizontal surface. Further, the above-mentioned left-right direction means a direction orthogonal to the up-down direction.
The cross-sectional area of the above-mentioned silicon tube refers to the area of the portion surrounded by the inner surface of the silicon tube in the cross section obtained by cutting the silicon tube in the direction orthogonal to the longitudinal direction thereof in the state where the solid preparation is not filled.
The cross-sectional area of the solid product refers to the area of the cross section of the solid product in a state of being filled in the silicon tube, which has the maximum area among the cross sections cut along the plane orthogonal to the longitudinal direction of the silicon tube.

Further, in the solid preparation of the present embodiment, the disintegration time measured using water as a solvent is 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 due to the ease of manufacturing the solid preparation. The disintegration time means the time until the sample in the solvent disintegrates. The procedure for measuring the disintegration time follows the method described in the "disintegration test method" of the item "6.09" in the 15th revised Japanese Pharmacopoeia. When a tablet having a tablet diameter of 3 to 15 mm, a tablet thickness of 4 to 7 mm, and a weight of 150 to 500 mg is used, it is preferable to use Toyama Sangyo Co., Ltd., model number: NT-400 as a disintegration tester. The solid preparation of the present embodiment preferably has a disintegration time of 0.01 minutes / mm or more and 25 minutes / mm or less, and more preferably 0.05 minutes / mm or more and 20 minutes / mm or less with respect to the thickness of the agent. It is more preferably 0.1 minutes / mm or more and 12 minutes / mm or less, further preferably 0.15 minutes / mm or more and 8 minutes / mm or less, and 0.2 minutes / mm or more and 4 minutes or less. Most preferably, it is / mm or less.

<Procedure for measuring collapse time>
One solid pharmaceutical product is placed in each of the glass tubes of the disintegration tester having six glass tubes. The upper and lower surfaces of each glass tube are open, and a stainless steel mesh having 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 solid preparation is placed in water at 37 ± 2 ° C., and the disintegration tester is operated. Observe the glass tube in the disintegration tester, and when it is confirmed that the solid product is about to disintegrate, pull up the glass tube and observe the disintegration of the solid product. Repeat this operation and observe until the solid product completely disintegrates. The time from when the disintegration tester is operated to the time when all six solid formulations disintegrate is measured, and the measured time is defined as the disintegration time. It should be noted that the solid product is considered to have disintegrated when no residue of the solid product is found in the glass tube, or when it is a soft substance that clearly does not retain its original shape even if it is found.

Examples of the solid preparation form of the present embodiment include tablets, capsules, pills, powders and the like, and the form of tablets or capsules is preferable. In either form, the gelling agent is present on the outermost surface of the solid formulation. The outermost surface portion refers to a portion located on the surface side of the solid preparation, and refers to a range of 0 mm or more and 1 mm or less from the surface of the solid preparation toward the center. It is particularly preferable that the solid preparation of the present embodiment has a gelling agent on the entire outermost surface portion thereof. In the present specification, if it can be confirmed that the gelling agent is present at two or more different locations on the outermost surface portion of the solid preparation, it can be said that the gelling agent is present on the entire outermost surface portion. Here, the presence of the gelling agent on the surface portion can be confirmed by scraping off about 30 mg of an arbitrary portion on the outermost surface portion of the solid preparation with a scalpel or the like and adding an appropriate amount of water to gel. For example, a solid preparation having a gelling agent on the entire outermost surface can be easily obtained as a tableted product of a mixed powder containing the gelling agent.

The solid product may or may not have a structure in which the surface portion and the portion on the central side thereof are distinguished from each other. For example, the solid product may have a multi-layer structure such as a nucleated tablet. Above all, when the solid preparation does not have a multi-layer structure and has a single-layer structure, it is preferable in terms of ease of production and the like.

The solid product may have a gelling agent at a portion other than the outermost surface portion. For example, the solid preparation may contain a gelling agent in both the outermost surface portion and the portion on the central side thereof (also referred to as the central portion). An example of such a solid preparation is a tablet having a single-layer structure bare tablet. In the solid preparation, the composition of the outermost portion and the composition of the central portion may be the same or different, but it is preferable that the composition is the same from the viewpoint of ease of producing a tablet having a naked tablet. The presence of the gelling agent in the central part of the solid preparation means that, for example, the solid preparation is cut in half with a cutter or the like, and about 30 mg of an arbitrary portion on the portion more than 1 mm from the surface of the solid preparation on the central side is cut with a scalpel or the like. It can be confirmed by scraping and gelling by adding an appropriate amount of liquid medium such as water. The components listed as disintegrants described later are not included in the gelling agent in the present application.

The case where the solid preparation of this embodiment is a tablet will be described.
The tablet is preferably a tablet having a naked tablet having a gelling agent. In general, a bare tablet (also referred to as an uncoated tablet) refers to a tablet having no coating layer formed on its surface. As used herein, the term "tablet having a bare tablet" means a tablet in which a coating layer is not formed on the surface of the tablet and the portion is in the state of a bare tablet (hereinafter, the tablet surface). The part where the coating layer is not formed is called the bare tablet part). Further, as used herein, the term "bare tablet" means a tablet in which a coating layer is not substantially formed on the surface (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, "naked tablet" is a concept included in "tablet having a naked tablet".

The tablet having the bare tablet of the present embodiment exhibits slimyness (also referred to as slipperiness) when a liquid medium such as water comes into contact with the bare tablet portion. It is preferable that the tablet having the naked tablet of the present embodiment has a gelling agent on the outermost surface portion of the naked tablet portion. The outermost surface portion refers to a portion of the bare lock portion located on the surface side, and refers to a range of 0 mm or more and 1 mm or less from the surface of the bare lock portion toward the center. The tablet of the present embodiment has a gelling agent on the bare tablet portion, particularly on the outermost surface portion of the bare lock portion, so that the tablet becomes slimy on the surface of the bare tablet portion when it comes into contact with a liquid medium such as water. As a result, the tablet having the naked tablet of the present 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 portion of the bare tablet portion. In the present specification, if it can be confirmed that the gelling agent is present at two or more different locations on the outermost surface portion of the bare tablet portion, it can be said that the gelling agent is present on the entire outermost surface portion of the bare tablet portion. Here, the presence of the gelling agent on the surface portion can be confirmed by scraping off about 30 mg of an arbitrary portion on the outermost surface portion with a scalpel or the like and adding an appropriate amount of a liquid medium such as water to gel. As will be described later, a tablet having a bare tablet having a gelling agent on the entire outermost surface portion of the bare tablet portion can be easily obtained as a tablet of a mixed powder containing the gelling agent.

Since the effect of the gelling agent is exerted by the presence of the bare tablet portion in the above-mentioned tablet having the bare tablet, 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, and particularly preferably 95% or more. Further, when the tablet having the bare tablet has a coating layer, the ratio of the tablet having the coating layer to the surface area of the tablet is preferably less than 30%, particularly preferably less than 10%, and substantially. Most preferably, there is no coating layer (meaning that the ratio of the area covered by the coating layer to the surface area of the tablet is less than 5%). When the tablet having the bare tablet has a coating layer, the thickness of the coating layer is preferably 3 mm or less, more preferably 2 mm or less, and 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 exerted, the manufacturing cost can be reduced, and the tablet can be prevented from becoming large in size. When the coating layer covers only a part of the tablet, the coating layer may be partially and continuously present, or may be dispersed in an island shape or the like. For example, if a powdery substance other than the gelling agent (for example, saccharides or other seasonings) is sprinkled on the surface of the bare tablet to the extent that a coating layer is present on a part of the surface of the tablet, the bare tablet portion is covered. It is acceptable because it works with the gelling agent present.

When the solid preparation of the present embodiment is a capsule, it is preferable that the capsule is coated with a coating layer containing a gelling agent. The gelling agent is preferably attached to the surface of the capsule film. For example, by mixing a powder containing a gelling agent with a soft capsule (soft capsule) or a hard capsule (hard capsule), the surface of the capsule can be coated with a coating layer. At this time, the adhesiveness may be improved by wetting the surface of the capsule with a solvent or the like. When the powder containing the gelling agent is difficult to adhere to the surface of the soft capsule or the hard capsule, the adhesiveness of the powder can be improved by wetting the surface of the capsule or the like. As another coating method, the surface of the soft capsule or the hard capsule can be coated by spraying a solution in which the gelling agent is dissolved. The capsule may be a hard capsule, but a soft capsule is particularly preferable. The range in which the surface of the capsule is covered with the coating layer is preferably 50% or more, more preferably 70% or more, further preferably 90% or more, and most preferably the entire surface.

When the solid preparation of the present embodiment is a pill, it is preferable that the pill has a bare pill containing a gelling agent. Such bare pills exhibit slimy properties when the surface comes into contact with water. Bare pills generally refer to pills that do not have a coating layer formed on their surface. Since the pill has a gelling agent in the bare pill, particularly on the outermost surface portion of the bare pill, the surface of the bare pill becomes slimy when it comes into contact with a liquid medium such as water. This makes the pills easier to swallow without the need for a coating layer. The pill, which is a bare pill, does not have a coating layer that covers the entire surface thereof, so that it has an advantage that the size of the pill can be prevented from becoming large and the manufacturing cost can be reduced.

When the solid preparation of the present embodiment is a powder, it is desirable that the powder is coated with a coating layer containing a gelling agent. For example, by spraying a solution containing a gelling agent on a powder as a core material, a powder having a part of the surface coated with a coating layer containing the gelling agent can be obtained.

In order to realize the above-mentioned sliminess and disintegration time, preferable components and compositions used in the solid preparation of the present embodiment will be described in detail below.
The following components and compositions of the solid preparation are the components and compositions contained in the tablet when the solid preparation is a tablet, and the components and composition contained in the capsule when the solid preparation is a capsule. In particular, it is preferable that the solid preparation is a tablet having a bare tablet, and the following components and composition of the solid preparation correspond to the components and composition contained in the bare tablet constituting the tablet.

A gelling agent is added to the solid preparation for the purpose of increasing the lubricity of the surface by contact with the aqueous liquid. As the gelling agent contained in the solid preparation, a substance that is powdery (particulate) and exhibits slimy properties when contained in a liquid medium such as water is used. Examples of the gelling agent 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, tragant gum, and karaya gum. , Cassia gum, lambzan gum, welan gum, macrohomopathy gum, curdran, purulan, gellan gum (deacylated gellan gum, native gellan lamb), pectin, and natural polysaccharides such as soybean polysaccharides; proteolytic products such as collagen; polyglutamic acid, etc. Polyamino acids; biopolymers such as polylactic acid, polyglutamic acid, and at least one selected from salts and derivatives thereof. Of these, natural polysaccharides are particularly preferable.
Examples of the derivative include hyaluronic acid derivative, alginic acid derivative, polyglutamic acid derivative and the like. Examples of the salt include alginate, hyaluronan, polyglutamic acid and the like. Examples of the hyaluronic acid derivative include hyaluronic acid ester and acetylated hyaluronic acid. Examples of the alginic acid derivative include alginic acid esters. Examples of the polyglutamic acid derivative include polyglutamic acid esters and the like. Examples of the alginate include sodium alginate, potassium alginate, ammonium alginate, calcium alginate and the like. Examples of the hyaluronate include sodium hyaluronate and potassium hyaluronate. Examples of the polyglutamate salt include sodium polyglutamate and potassium polyglutamate. Only one type of gelling agent may be used alone, or two or more types may be used in combination.

Gelling agents include locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, gum arabic, gati gum, tragant gum, karaya gum, cassia gum, lambzan gum, welan gum, macrohomopsis gum, It is preferable to contain curdran, purulan, gellan gum, polyamino acid, polylactic acid, and one or more selected from these salts and derivatives (hereinafter, also referred to as specific gelling agents) in that they easily disintegrate in the body after ingestion. In particular, it is preferable to contain locust bean gum in that it is excellent in disintegration after ingestion and that both disintegration and sliminess are exhibited at a high level.
Further, it is also preferable to combine two or more kinds of gelling agents from the viewpoint of achieving both disintegration property and slimy property and from the viewpoint of manufacturability, and a specific gelling agent and a gelling agent other than the specific gelling agent are combined. 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 xanthan gum or guar gum with locust bean gum, the ease of swallowing due to a slimy feeling can be effectively enhanced. Further, by combining guar gum with locust bean gum, a solid preparation having excellent disintegration in the body after ingestion can be obtained.

In the solid preparation, the proportion of the gelling agent is preferably 0.01% by mass or more in order to sufficiently give a slimy feeling when in contact with a liquid medium such as water. Further, the proportion of the gelling agent in the solid preparation is preferably 70% by mass or less from the viewpoint of ease of elution of the active ingredient. From these points, the proportion of the gelling agent in the solid preparation is more preferably 0.1% by mass or more and 60% by mass or less, further preferably 1% by mass or more and 50% by mass or less, and 3% by mass. It is even more preferably 30% by mass or more, and most preferably 5% by mass or more and 20% by mass or less. When the solid preparation of the present embodiment contains at least one selected from the specific gelling agent in the solid preparation, the gel is preferably in the preferred range of the total mass of the specific gelling agent in the solid preparation. The same range as the preferable range of the agent can be mentioned. Here, the total mass of at least one selected from the specific gelling agent is the mass of one of the solid preparations when the solid preparation contains only one selected from the specific gelling agent, and is a solid. If the pharmaceutical product contains two or more of these, it is the total mass of them.

When the solid preparation of the present invention contains a specific gelling agent and other gelling agents, the ratio of the former to the latter in the solid preparation is 100% by mass of the latter from the viewpoint of achieving both sliminess and disintegration. 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, and particularly preferably 20 parts by mass or more and 800 parts by mass or less.

For example, when the solid preparation of the present invention contains xanthan gum and locust bean gum, the ratio of the former to the latter in the solid preparation increases the sliminess and the content of the active ingredient, so that the ratio is based on 100 parts by mass of xanthan gum. The locust bean gum is more preferably 10 parts by mass or more and 1000 parts by mass or less, further 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.

When the solid preparation of the present invention contains guar gum and locust bean gum, the ratio of the former to the latter in the solid preparation increases the sliminess and the content of the active ingredient, and thus locusts with respect to 100 parts by mass of guar gum. The bean gum is more preferably 10 parts by mass or more and 1000 parts by mass or less, further 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.

The solid preparation is one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, celluloses, cellulose derivatives, starches, starch derivatives and starch decomposition products (hereinafter, these are also referred to as specific excipients). Is preferably contained. By combining the gelling agent with these specific excipients, a solid preparation having excellent sliminess and a short disintegration time can be obtained.

Specific excipients include (A) monosaccharides, (B) disaccharides, (C) oligosaccharides, (D) cellulose, (E) cellulose derivatives, (F) starch, (G), as described above. One or more selected from starch derivatives and (H) starch decomposition products may be included, but among the components described in (A) to (H), in order to achieve both disintegration and sliminess. , It is preferable to contain two or more components belonging to different categories in combination. Specific examples thereof include a combination of disaccharide and cellulose, a combination of disaccharide and reduced maltose, and a combination of disaccharide and starch. Further, among the components described in (A) to (H), it is more preferable to contain 3 or more components belonging to different categories in combination. Specific examples thereof include a combination of disaccharide, starch and cellulose, a combination of disaccharide, reduced maltose and cellulose and the like.

Examples of sugar alcohols include monosaccharide alcohols, disaccharide alcohols, and trisaccharide or higher alcohols. Examples of the monosaccharide alcohol include erythritol, D-treitol, tetritor such as L-treitol, pentitol such as D-arabinitol and xylitol, D-iditol, galactitol (darsitol), D-glucitol (sorbitol) and the like. Examples thereof include hexitol, cyclitol such as inositol, mannitol, volemitol, ribitol, persitol, D-erythritol-D-galacto-octitol and the like. Examples of the disaccharide alcohol include reduced maltose (maltitol), lactitol, and reduced palatinose (isomalt). Examples of alcohols having a trisaccharide or higher include maltotriitol, isomalttotriitol, panitol and the like. The sugar alcohol may be at least one selected from disaccharide alcohols, particularly from the viewpoint of manufacturability such as obtaining the hardness of tableted tablets in combination with the gelling agent used in the present invention. It is preferable, in particular, at least one selected from reduced maltose and reduced palatinose.

Examples of monosaccharides include glucose, galactose, fructose and mannose. Among these, glucose is preferable in terms of availability and compatibility between disintegration and sliminess.

Examples of the disaccharide include sucrose, maltose, lactose (lactose), trehalose, turanose, and cellobiose. Among these, one or more selected from trehalose, sucrose, and maltose are preferable from the viewpoint of disintegration, and sucrose and maltose are more preferable from the viewpoint of easy availability and compatibility between disintegration and sliminess. Although the effect of the present invention can be obtained even when lactose is contained, the disaccharide is more preferably a disaccharide other than lactose from the viewpoint of achieving both disintegration and sliminess.

Examples of oligosaccharides include those having trisaccharides or more and 20 sugars or less, preferably trisaccharides or more and 10 sugars or less, more preferably trisaccharides or more and hexasaccharides or less, specifically, raffinose, maltotriose, and the like. Examples thereof include melesitos, gentianose, acarbose, stachiose, galactooligosaccharides, fructo-oligosaccharides, mannan oligosaccharides, isomalto-oligosaccharides (isomaltotriose, panose), xylooligosaccharides, soybean oligosaccharides, nigerooligosaccharides and milk fruit oligosaccharides. In particular, it is preferable to use an isomaltooligosaccharide or a fructooligosaccharide in terms of easy availability, disintegration property and slimy property.

It is preferable that the solid preparation contains any one of a monosaccharide, a disaccharide, and an oligosaccharide from the viewpoint of masking the taste and promoting saliva secretion. In particular, it is preferable that the solid preparation contains these saccharides on the surface portion.

Examples of cellulose include powdered cellulose and crystalline cellulose. Crystalline cellulose is obtained by partially depolymerizing α-cellulose obtained as pulp from a fibrous plant with an acid and purifying it. For example, those corresponding to crystalline cellulose described in the 15th revised Japanese Pharmacopoeia Manual (published by Hirokawa Bookstore) 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 solid preparation of the present invention.

Examples of the cellulose derivative include carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and methyl cellulose. Carboxymethyl cellulose having a degree of etherification of 0.2 mol / C6 to 1.0 mol / C6 is preferable in terms of easy availability, sliminess and disintegration time, and 0.5 mol / C6 to 0. It is more preferably 8 mol / C6. Although the effect of the present invention can be obtained even when croscarmellose sodium obtained by internally cross-linking sodium carboxymethyl cellulose or hydroxypropyl cellulose having a low degree of substitution is contained, a cellulose derivative can be obtained from the viewpoint of achieving both disintegration and sliminess. More preferably, it is a cellulose derivative other than croscarmellose sodium and low-degree-of-substitution hydroxypropyl cellulose.

Examples of starch include natural starch. Examples of the origin of starch include corn, potato, kudzu, tapioca, kansho, rice, wheat, wheat, barley, yam, and taro. When starch is blended, it is particularly preferable to blend it in combination with sugar alcohol in order to achieve both disintegration and sliminess.

Starch derivatives include chemical starch, oxidized starch, enzyme-treated starch, pregelatinized starch, phosphate starch, phosphate distarch, acetate starch, octenyl succinate starch, glycerol distarch, carboxymethyl starch, hydroxypropyl starch, bridge starch, and soluble starch. Examples thereof include starch, grafted starch and sodium carboxymethyl starch, and pregelatinized starch is preferable in terms of both sliminess and disintegration time. When a starch derivative is blended, it is particularly preferable to blend it in combination with a sugar alcohol in order to achieve both disintegration and sliminess. Although the effect of the present invention can be obtained even when sodium carboxymethyl starch is contained, the starch derivative is a starch derivative other than sodium carboxymethyl starch from the viewpoint of achieving both disintegration and sliminess. Is more preferable.

Examples of the starch decomposition product include dextrin, and those having a DE of 8 to 9.5 are preferably mentioned.

The content of the specific excipient in the solid preparation is 10 parts by mass or more with respect to 100 parts by mass of the gelling agent in the naked tablet, which is an effect of using the gelling agent and the specific excipient in combination. 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 naked tablet from the viewpoint of increasing the content of the active ingredient. preferable. From these points, the amount of the specific excipient in the solid preparation is preferably 10 parts by mass or more and 3000 parts by mass or less, and 20 parts by mass or more and 2500 parts by mass with respect to 100 parts by mass of the gelling agent in the solid preparation. The amount is more preferably 30 parts by mass or more, and particularly preferably 2000 parts by mass or less.

The amount of the excipient is preferably 1 part by mass or more and 90 parts by mass or less, more preferably 2 parts by mass or more and 80 parts by mass or less, and most preferably 3 parts by mass or more with respect to 100 parts by mass of the solid preparation. It is also preferable that the amount is 70 parts by mass or less. In particular, from the viewpoint of disintegration, the specific excipient preferably occupies 40% by mass or more, more preferably 50% by mass or more, and further preferably 60% by mass or more in the solid preparation. , 70% by mass or more. The upper limit of the amount of the specific excipient is preferably 95% by mass or less in the solid preparation from the viewpoint of containing the gelling agent, and more preferably 90% by mass or less.

The solid preparation in the present invention may contain at least one selected from monosaccharides, disaccharides, oligosaccharides, starch derivatives (particularly pregelatinized starch) and starch decomposition products among specific excipients. It is preferable because it has high sliminess, and it is more preferable to contain monosaccharides, disaccharides, oligosaccharides or starch decomposition products.

In particular, the solid preparation contains monosaccharides, disaccharides, oligosaccharides, sugar alcohols, crystalline celluloses or cellulose derivatives (particularly carboxymethyl cellulose) as specific excipients, which is excellent in disintegration property in addition to sliminess. Therefore, it is more preferable to contain monosaccharides, disaccharides, oligosaccharides, sugar alcohols or carboxymethyl cellulose.
In addition, the inclusion of sugar alcohol and disaccharide enhances the binding property of the raw material powder of the solid preparation, and when the solid preparation is a tablet, the ease of preparation such as the hardness of the tableted tablet can be obtained. It is also preferable in that the unpleasant taste masking effect of the active ingredient can be obtained.

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

In addition, the solid preparation may contain a combination of a disaccharide and one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starches and starch decomposition products as specific excipients, which is disintegrating and slimy. From the viewpoint of improvement, a combination of disaccharide and an oligosaccharide or a cellulose derivative is particularly preferable. When the naked tablet contains a disaccharide in combination with another specific excipient as a specific excipient, from the viewpoint of achieving both sliminess and disintegration, the uncoated tablet is based on 100 parts by mass of the disaccharide. The other specific excipient is more preferably 1 part by mass or more and 1000 parts by mass or less, further 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. Is particularly preferable.

Further, it is preferable that the solid preparation contains a sugar alcohol in combination with starch or pregelatinized starch as a specific excipient from the viewpoint of improving disintegration and sliminess. When the solid preparation contains sugar alcohol in combination as a specific excipient, starch or pregelatinized starch, starch is added to 100 parts by mass of sugar alcohol from the viewpoint of achieving both sliminess and disintegration. Alternatively, the pregelatinized starch is more 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 particularly preferably 50 parts by mass or more and 500 parts by mass or less.

In this embodiment, starch, a starch derivative or a starch decomposition product is contained, and the combination thereof with xanthan gum, locust bean gum and guar gum and salts and derivatives thereof, particularly locust bean gum, balances hardness with the degree of gelation. It is preferable in that it is easier to obtain a solid preparation that is easy to swallow.
Further, as will be described later, sugar alcohols can be obtained from xanthan gum, locust bean gum, guar gum, salts and derivatives thereof under the condition that the surface is coated with a gelling agent and does not contain particles containing the gelling agent. Combining with at least one selected is also preferable in that it is excellent in hardness, ease of drinking and slipperiness, and it is easier to obtain a solid preparation that is easy to swallow. Further, as described later, under the condition that the coating layer of the gelling agent is not contained, the gelling agent composed of starch and xanthan gum, locust bean gum or guar gum, and at least one selected from salts and derivatives thereof. It is also preferable that it is a solid preparation containing reduced maltose.

It is preferable that the solid preparation contains a specific excipient on the outermost surface, and when the solid preparation is a tablet having a bare tablet, it is preferable that the solid preparation also contains a specific excipient at the center.

3. 3. Other components The solid preparation preferably contains silicon dioxide or the like as a fluidity improving agent. 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, and more preferably 0.1 parts by mass or more and 1.8 parts by mass with respect to 100 parts by mass of the solid preparation. It is 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 that the solid preparation contains a lubricant in terms of improving manufacturability (preventing pestle only during tableting). Examples of the lubricant include magnesium stearate and calcium stearate. When the lubricant is contained, the proportion thereof 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 in the solid preparation of the present invention. preferable.

The solid preparation may contain an active ingredient. The active ingredient referred to here may be a drug, a functional ingredient other than the drug, a processed product derived from a plant, an animal, a microorganism, or the like. The solid preparation may contain the above-mentioned active ingredient, a specific excipient, silicon dioxide, a disintegrant, a lubricant, a saccharide, a binder, a seasoning other than the saccharide, an emulsifier, a fragrance and the like. Further, the solid preparation of the present embodiment is for oral use, that is, for internal use, and is a tablet for swallowing. Needless to say, the solid preparation of the present embodiment may be used as a supplement, a health food, a nutritionally functional food, a food with a functional claim, a food for specified health use, and a pharmaceutical product.

The solid preparation of the present embodiment contains a seasoning other than saccharides and / or a fragrance on the outermost surface, thereby promoting saliva secretion when the solid preparation is contained in the oral cavity, and water to the solid preparation. It is possible to increase the supply of liquid media such as. As the seasoning, a sweetener, an acidulant or the like can be used. As the sweetener, a sucralose sucrose derivative, a peptide-based sweetener such as aspartame, alitame, neotame, or glycyrrhizin, stevia, kanzo, or the like can be used. As the acidulant, an organic acid can be used, and examples thereof 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 and the like can be used.

The solid pharmaceutical product according to this embodiment may contain a disintegrant. Examples of the disintegrant include baking soda (sodium hydrogen carbonate), magnesium carbonate, carmellose calcium, sodium starch glycolate and the like, which can be used as food additives, crospovidone, sodium carboxymethyl starch, croscarmellose sodium, and low. Substitution degree hydroxypropyl cellulose can be mentioned. Although the effect of the present invention is exhibited even when a disintegrant is contained, it is preferable that the content of the disintegrant is small from the viewpoint of excellent sliminess, and specifically, with respect to 100 parts by weight of the solid preparation. The blending amount of the disintegrant is preferably 9.9 parts by weight or less, more preferably 9 parts by weight or less, further preferably 6 parts by weight or less, still more preferably 3 parts by weight or less, particularly preferably 1 part by weight or less, and non- Most preferably, it is contained.

Among the above-mentioned disintegrants, one or more disintegrants selected from crospovidone, sodium carboxymethyl starch, sodium croscarmellose or low-degree-of-substitution hydroxypropyl cellulose from the viewpoint of excellent sliminess (hereinafter, these are specific disintegration agents). It is preferable that the content of the agent) is small. Specifically, the blending amount of the disintegrant is preferably 9.9 parts by weight or less, more preferably 9 parts by weight or less, still more preferably 6 parts by weight or less, and 3 parts by weight or less with respect to 100 parts by weight of the solid preparation. Even more preferably, it is extremely preferably 1 part by weight or less, and most preferably it is not contained. Hydroxypropyl cellulose having a low degree of substitution is produced by reacting propylene oxide with alkaline cellulose at a high temperature, and those dried at 105 ° C. for 1 hour contain 5.0 to 16.0% of hydroxypropyl groups. Means to include.

The solid preparation according to the present embodiment may contain particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent. The effect of the present invention is exhibited even when the surface contains sugar alcohol coated with the gelling agent and particles containing the gelling agent, but the surface is coated with the gelling agent from the viewpoint of excellent disintegration property. It is preferable that the content of the particles containing the sugar alcohol and the gelling agent is small, and the blending amount of the particles containing the sugar alcohol and the gelling agent whose surface is coated with the gelling agent is 100 parts by weight of the solid preparation. It is preferably 10 parts by weight or less, more preferably 5 parts by weight or less, further preferably 3 parts by weight or less, still more preferably 1 part by weight or less, and most preferably not contained. The sugar alcohol whose surface is coated with the gelling agent and the particles containing the gelling agent are formed by spraying the gelling agent on the particles containing the sugar alcohol. In the present invention, the solid preparation does not contain particles containing sugar alcohol and a gelling agent whose surface is coated with a gelling agent, and the gelling agent and a specific excipient are uniformly mixed. By doing so, it becomes easier to shorten the decay time.

The fact that the surface is free of sugar alcohol and particles containing the gelling agent is confirmed by examining the distribution of the gelling agent in the solid preparation by cross-sectional imaging such as TOF-SIMS. can do. At this time, if the gelling agent is uniformly dispersed in the solid preparation without observing the layer in which the gelling agent is locally concentrated, the surface of the solid preparation of the present invention is the gelling agent. It can be said that the particles containing the sugar alcohol and the gelling agent coated with the gel are not contained.

Considering the ease of swallowing as the solid preparation, 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 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 later.

Hereinafter, a suitable method for producing the solid pharmaceutical product of the present embodiment will be further described.
The production method of the present embodiment is a gelling agent and one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, celluloses, cellulose derivatives, starches, starch derivatives and starch decomposition products (specific excipients). ), And it is preferable to produce a tablet, particularly a tablet having a bare tablet, by this method.
Examples of the gelling agent, sugar alcohol, monosaccharide, disaccharide, oligosaccharide, cellulose, cellulose derivative, starch, starch derivative and starch decomposition product include those described above. In addition, as components other than the gelling agent and the specific excipient in the powder containing the gelling agent and the specific excipient, the excipients, disintegrants, binders, lubricants, emulsifiers, and effectives mentioned above are used. Ingredients, seasonings, fragrances and the like can be mentioned. The preferable range of the mass ratio of the gelling agent in the raw material powder, the preferable mass ratio of the preferable gelling agent component, the preferable mass ratio of the specific excipient, and the preferable mass ratio of the silicon dioxide, the disintegrant, and the lubricant are , These are the same as the preferable mass ratios in the above-mentioned solid preparation.

Further, as described above, when the tablet is nucleated, the raw material powder containing an arbitrary nucleus is tableted as the raw material powder.

The raw material powder containing the gelling agent and the specific excipient may be a mixture of the powdered gelling agent, the specific powdered excipient and other powdery components contained as needed. It may be a granulated powder obtained by granulating a mixture of a powdery gelling agent, a specific powdery excipient, and other powdery components contained as necessary.
As the granulation method, a known granulation method used for producing an oral tablet by a granulation tableting method can be used without particular limitation.

A suitable method for producing the solid preparation of the present embodiment is preferably in a gelling agent powder and a sugar alcohol, a monosaccharide, a disaccharide, an oligosaccharide, a cellulose, a cellulose derivative, a starch, a starch derivative and a starch decomposition product. The present invention comprises a step of mixing with one or more kinds of powders selected from the above, and a step of tableting the obtained mixed powder without spraying an aqueous solution in which a gelling agent is dissolved. As described above, this gels without such a coating layer as compared with the solid preparation obtained by tableting the particles containing the sugar alcohol and the gelling agent whose surface is coated with the gelling agent. This is because a solid preparation in which the agent is uniformly mixed with a specific excipient, particularly a bare tablet, is superior in terms of disintegration and sliminess, especially disintegration.

As described above, the solid preparation of the present embodiment is a mixed powder tablet containing a gelling agent and a specific excipient, particularly the mixed powder obtained without spraying an aqueous solution containing the gelling agent. A tableted product obtained by tableting the mixed powder is preferable because a solid preparation in which the gelling agent is present on the entire surface thereof can be easily obtained. "Mixed powder tablet containing gelling agent and specific excipient" and "Mixed powder (including gelling agent and specific excipient) are obtained without spraying an aqueous solution containing gelling agent. , A tableted product obtained by tableting the mixed powder, even if the production method is included, the present form of the gelling agent or a specific excipient in the naked tablet is described in the present specification. However, it was not realistic to specify it in more detail, and there was an impossible situation in which such an expression had to be taken.

The solid preparation of the present embodiment is a solid preparation to be orally ingested, and the surface lubricity is increased by contact with an aqueous liquid. In particular, when the solid preparation is a tablet having a bare tablet as described above, the naked tablet contains a gelling agent as described above, so that it is the same as a tablet having a bare tablet containing no gelling agent during storage. Although it has a hard property, it has a slimy feeling, flexibility and elasticity when it comes into contact with a liquid medium such as water when it is taken, and its surface becomes gelled, making it easy to swallow. In addition, the shape of the bare tablet portion is maintained when it comes into contact with a liquid medium such as water, and the active ingredient and the like present in the bare tablet portion are suppressed from dissolving in the oral cavity. As described above, the solid preparation of the present embodiment has a characteristic that it swells with a liquid medium such as water to give a slimy feeling to the surface of the naked tablet.

As described above, preferable forms of the tablet of the present invention include, for example, the following.

(1) Gelling agent and
A tablet having a bare tablet containing one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, celluloses, cellulose derivatives, starches, starch derivatives and starch decomposition products.

(2) The tablet according to (1), wherein the bare tablet contains one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides and starch decomposition products.

(3) The gelling agent is 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, tragant gum, etc. Polysaccharides such as gum arabic, cassia gum, lambzan gum, welan gum, macrohomopsis gum, curdlan, purulan, gellan gum (deacylated gellan gum, native gellan lamb), pectin, and soybean polysaccharides; protein degradation products such as gelatin and collagen; poly The tablet according to (1) or (2), which is at least one selected from polyamino acids such as glutamate; biopolymers such as polylactic acid and polyglutamic acid, and salts and derivatives thereof.

(4) The tablet according to any one of (1)-(3), excluding the tablet obtained by tableting the granulated particles by spraying an aqueous solution in which the gelling agent is dissolved.

(5) The tablet according to any one of (1)-(4), excluding those containing crospovidone, sodium carboxymethyl starch, sodium croscarmellose or low-degree-of-substitution hydroxypropyl cellulose.

(6) Gelling agent and
The tablet according to any one of (1)-(5), which comprises a bare tablet containing at least one selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starch and starch decomposition products.

(7) Locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, arabic gum, gati gum, tragant gum, karaya gum, cassia gum, lambzan gum, welan gum, macrohomopsis gum, curdlan, Pullulan, gellan gum, polyamino acids, polylactic acid, and one or more selected from these salts and derivatives.
The tablet according to any one of (1)-(6), which comprises a bare tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starch and starch decomposition products.

(8) Locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, arabic gum, gati gum, tragant gum, karaya gum, cassia gum, lambzan gum, welan gum, macrohomopsis gum, curdlan, Pullulan, gellan gum, polyamino acids, polylactic acid, and one or more selected from these salts and derivatives.
One or more selected from xanthan gum, guar gum, alginic acid, carrageenan,
The tablet according to any one of (1)-(7), which comprises a bare tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starch and starch decomposition products.
tablet.

(9) Gelling agent and
With disaccharides
The tablet according to any one of (1)-(8), which comprises a bare tablet containing one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starches, and starch decomposition products.

(10) Gelling agent and
With sugar alcohol
Contains one or more selected from starch and pregelatinized starch
The tablet according to any one of (1)-(9), which does not contain a coating layer of a gelling agent.

Hereinafter, the present invention will be described in more detail with reference to examples. However, the scope of the present invention is not limited to such examples. Commercially available products were used as the materials shown in Table 1-3. In particular, as the isomalt oligosaccharide, isomalt 900P manufactured by Showa Sangyo Co., Ltd. was used. As the crystalline cellulose, KC Flock W-400G manufactured by Nippon Paper Industries, Ltd. was used. As the carboxymethyl cellulose, calcium carboxymethyl cellulose having a degree of etherification of 0.5 to 0.7 mol / C6 was used. As the starch powder, a perfiller 102 manufactured by Freund Sangyo Co., Ltd. was used. As the pregelatinized starch, NON-GMO corn alpha-Y manufactured by Sanwa Cornstarch Co., Ltd. was used. As the dextrin, Max 1000 manufactured by Matsutani Chemical Industry Co., Ltd. was used.

1. 1. Evaluation of sliminess [Example 1]
As the raw material powder, 400 raw materials (excluding calcium stearate) were mixed in a plastic bag according to the blending ratio in Table 1, passed through a sieve, and calcium stearate was further added and mixed. This mixed powder was directly locked with a rotary locking machine (Kikusui Seisakusho) to obtain a disk-shaped bare lock. The hardness of the obtained bare tablet was measured with a Schleunigel tablet hardness tester. Further, when the tablet diameter (diameter) and the tablet thickness of the obtained bare tablet were measured with a digital caliper (Digimatic Caliper CD-15AX; Mitutoyo), the hardness was 7.4 kgf, the tablet diameter was 10 mm, and the tablet thickness was 3.52 mm. rice field. The weight of one of the obtained naked tablets was measured and found to be 270 mg. The hardness, tablet diameter, tablet thickness and weight are average values of the measured values of each of the three grains.

[Example 2]
A naked tablet was obtained in the same manner as in Example 1 except that the compounding ratio of the raw material powder was changed according to the compounding ratio in Table 1. When the same measurement as in Example 1 was performed on the obtained naked tablet, the hardness was 7.7 kgf, the lock diameter was 10 mm, the lock thickness was 3.50 mm, and the weight was 270 mg.

[Evaluation of Examples 1 and 2]
For the naked tablets obtained in Examples 1 and 2, the measurement of the myoelectric potential of the throat at the time of administration and the questionnaire on the feeling of administration were performed by a single-blind crossover.
In addition, the slope sliding time was measured to evaluate the slipperiness of the tablets.

-How to take naked tablets The subjects selected 6 healthy adults who were aware that they were not good at taking tablets (male / female ratio 2: 4). The method of administration was to first contain 4 target naked tablets in the mouth, then 20 mL of water at 22 ° C. in the mouth, and then take the naked tablets together with water.

-Measurement of myoelectric potential For myoelectric potential measurement, an electromyogram (wireless myoelectric measurement / analysis system "Lateo" manufactured by AM Science Co., Ltd.) was used. The measurement method was according to the manual attached to the EMG, but specifically, it was performed as follows. The electrodes of the EMG were attached to the throat, and the subject was given 20 mL of water, which was the same amount as when taking the naked tablet, in order to acclimatize the throat. Next, the myoelectric potential of the throat when 20 mL of water was taken was measured. Then, after containing 4 naked tablets in the mouth, the myoelectric potential of the throat when taken with 20 mL of water was measured for each test group. For the muscle activity amount, the relative value when the muscle activity amount when only water was taken was set to 100 (%) was obtained from the integrated value calculated based on the obtained myoelectric potential (unit volt (V)). .. The value obtained by adding up the relative values once per person and dividing by the number of people was taken as the amount of muscle activity (%). In addition, 1Count is 1/200 second in FIGS. 1 to 3.
The measurement of each test group was performed with a rest time of about 5 minutes, and the order of taking the naked tablets was changed for each subject.

・ Questionnaire For slipperiness, the lowest rating (-3 points) was given when the tablet was caught when the tablet was taken and there was no slippage to the extent that it did not go through the throat and it was difficult to swallow. The highest rating (3 points) was given to the case where it was slippery and easy to drink so that it would not get caught.
For stickiness, the lowest rating (-3 points) is when it is sticky to the extent that it feels sticky on the tongue or pharynx and it is difficult to drink. It was evaluated on a 7-point scale with the highest evaluation (3 points).

-Aluminum channel with a U-shaped cross section (straight in side view, channel length 90 cm, width 1.2 cm) fixed at an inclination of 30 ° was supplied with 150 ml of water per minute from the upper part of the channel. 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 to slide 80 cm to the lower end was measured. The test was performed 5 times, and the average value of the 5 times was calculated and used as the slope sliding time (seconds).

The amount of muscle activity (%) of the throat obtained by measuring the myoelectric potential is shown in Table 1, and typical electromyograms are shown in FIGS. 2 to 4.
Table 1 shows the average values of 6 people and the measurement results of the slope sliding time (seconds) for the evaluation points obtained by the questionnaire. In Table 1, the unit of composition of the naked tablet is parts by mass.

As is clear from Tables 1 and 2 to 4, the naked tablets of Examples 1 and 2 suppressed the increase in throat muscle activity by about 1.5 times as compared with the case of taking only water. It is a naked lock that does not require force when taken, is less likely to feel swallowing stress, and is easy to swallow. The questionnaire also shows that while feeling slippery, the bare lock does not stick to the tongue or pharynx, making it easy to swallow.
In addition, in the naked tablet containing crospovidone, sodium carboxymethyl starch, sodium croscarmellose or low-degree-of-substitution hydroxypropyl cellulose, the slipperiness and the non-stickiness are reduced as compared with Example 1 or 2.

Further, when comparing the slope sliding times, as shown in Table 1, since Examples 1 and 2 slide down in 2 seconds or less, the bare lock of Example becomes slippery when it comes into contact with water, so that it is easy to swallow. You can see that it is a thing.
In addition, the naked tablet containing crospovidone, sodium carboxymethyl starch, sodium croscarmellose or low-degree-of-substitution hydroxypropyl cellulose has lower slope slipperiness as compared with Example 1 or 2.

From the above, in the case of naked 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 less resistance. rice field.

2. 2. Evaluation of disintegration [Examples 3 to 6]
According to the compounding ratio in Table 1 below, the hardness is 9 kgf, the tablet diameter is 9 mm, and the tablet thickness is 4.81 to 5.08 mm (4.81 mm in Example 3, 4.89 mm in Examples 4 and 6, and 5 in Example 5). A naked tablet was obtained in the same manner as in Example 1 except that the weight was changed to 300 mg (.08 mm).
The disintegration time of the obtained naked tablets was measured by the following method. The results are shown in Table 2.

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

The unit in the composition of Table 2 is a part by mass.

As is clear from Table 2, it was found that the naked tablet containing the gelling agent and a specific disintegrant (sugar alcohol, cellulose, cellulose derivative, starch) had a short disintegration time. Further, even when a specific disintegrant (crosspovidone) was blended, the disintegration time was only shortened by about 20% as compared with the case where it was not blended.

3. 3. Evaluation of sliminess and disintegration time [Examples 7-14, 16-21, Comparative Example 1]
Naked tablets were obtained in the same manner as in Example 1 according to the compounding ratios 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 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 put into a fluidized layer granulator (fluid layer granulation drying / coating machine model: FD-LAB-1, Paulec), and a suspension of crystalline cellulose was added. After spraying, the particles are further granulated by spraying a suspension of xanthan gum diluted with hot water to 0.1% (w / v), and a coating layer of xanthan gum is formed on the surface of the particles composed of a mixed powder of sorbitol and maltose. The formed particle composition (particles containing sugar alcohol and a gelling agent whose surface was coated with a gelling agent) was obtained.
After 0.5 parts by mass of calcium stearate is mixed with the obtained particle composition, the product is locked using a rotary tableting machine (Kikusui Seisakusho), and the hardness, tablet diameter, and tablet thickness are all the same as those of Examples 3 to 5. A naked tablet weighing 300 mg was obtained. The amounts of crystalline cellulose and xanthan gum in the naked tablet were the amounts shown in Table 1.

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

Further, the maximum stress was measured for the bare locks obtained in Examples 7 to 21 and Comparative Example 1 by the following method.

<Measurement procedure of maximum stress>
The bare lock was allowed to stand on a plastic substrate, and 0.2 μL of water at 25 ° C. was dropped with a dropper per 1 mm ² of the surface area of the bare lock and held in that state for 15 seconds.
A silicon tube with an inner diameter of 9 mm and an outer diameter of 11 mm, which is arranged along the vertical direction so that the longitudinal direction coincides with the vertical direction and is fixed so as to be movable in the vertical direction, and fixed with the silicon tube sandwiched in the left-right direction. Using the pair of slits formed therein, one grain of the bare tablet (lock diameter 9 mm) was filled under the slit in the silicon tube. The maximum stress when the silicon tube is moved upward by 20 mm at a speed of 0.5 mm / sec with respect to the bare lock along the slit is measured using a creep meter manufactured by Yamaden Co., Ltd. (RE2-33005C). did. The cross-sectional area of the silicon tube used for the measurement was 50% of the cross-sectional area of the bare lock. If the stress exceeds 20, the measurement is finished at that point. As the silicon tube, a clear silicone square tube manufactured by Fuso Rubber Industry Co., Ltd. was used. As a slit, a special cylindrical extrusion jig (AT-43446) manufactured by Yamaden Co., Ltd. was used, and this was fixed at a position where the minimum distance between them was 2 mm.
The maximum stress was calculated as the average value of the triplets.

The unit in the composition of Table 3 is a part by mass.

As can be seen from the comparison between Examples 7 to 21 and Comparative Example 1 in Table 3, the gelling agent and the specific one are as opposed to the naked tablet of Comparative Example 1 containing only a specific excipient and not containing a gelling agent. In the naked tablets of Examples 7 to 21 containing the excipient of, the maximum stress is greatly reduced.
Further, from the results of Examples 7 to 14, it can be seen that among the specific excipients, the maximum stress is particularly low in the case of a naked tablet containing a monosaccharide, a disaccharide, an oligosaccharide or a starch decomposition product.

Further, from the comparison of Examples 15 and 16, the sugar alcohol was used as the gelling agent as compared with the bare tablet obtained by tableting the particles containing the sugar alcohol and the gelling agent whose surface was coated with the gelling agent. It can be seen that the disintegration time and the maximum stress of the bare tablets mixed and beaten are shortened.

In addition, compared to the bare tablet obtained by tableting the sugar alcohol whose surface is coated with the gelling agent and the particles containing the gelling agent, the bare tablet obtained by mixing the sugar alcohol with the gelling agent and tableting the tablet. The tendency for the disintegration time to be shorter and the maximum stress to be lower is observed not only when sorbitol is used as the sugar alcohol, but also for sugar alcohols other than sorbitol (erythritol, mannitol, etc.).

Further, from the results of Examples 17 to 21, when locust bean gum is used as the gelling agent, the disintegration time is particularly short and the maximum stress is low. Therefore, from the viewpoint of achieving both disintegration and sliminess. It can be seen that locust bean gum is particularly excellent among gelling agents.

The following naked tablets (Prescription Examples 1-41) were produced in the same manner as in Example 1. All of the naked tablets were excellent in sliminess and disintegration. In particular, bare tablets containing two or more gelling agents combined, bare tablets containing one or more selected from monosaccharides, disaccharides, oligosaccharides, starch derivatives and starch degradation products, specific excipients. Bare tablets and disaccharides containing two or more components belonging to different categories in combination with one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch and starch decomposition products are excellent. It was excellent in sliminess and disintegration. Further, the bare tablets prepared in Formulation Examples 1-41 are sprinkled with sucrose, and the ratio of sucrose covered by the coating layer in the tablet surface is adjusted to be 20% or more and less than 30% (sucrose is prepared using water). The tablets having bare tablets (the ratio was adjusted by adhering) were also excellent in sliminess and disintegration. Similarly, a bare tablet prepared so that the ratio of the coating layer to the surface area of the tablet to be covered by the coating layer was 5% or more and less than 10% was also excellent in sliminess and disintegration.

Prescription example 42
Prepare the content liquid (95% by mass of safflower oil, 5% by mass of beeswax), and the ratio of glycerin 16.4% by mass, purified water 36.8% by mass, gelatin 43.3% by mass and caramel dye 3.5% by mass. It was made into a soft capsule by filling the capsule film (weight before drying) contained in. Encapsulation was carried out by casting the capsule film solution to form a film, filling the inside with the content solution, heat-sealing, and drying the molded soft capsule (300 mg per capsule). The soft capsule and the locust bean gum were mixed so that the weight of the locust bean gum (powder) was 5 mg with respect to one soft capsule, and the locust bean gum was attached. By this step, a soft capsule in which a gelling agent was attached to a part of the surface was obtained.

Since the solid preparation of the present invention is easy to swallow and does not need to be coated on the entire surface, it is possible to avoid an increase in size due to coating, and it is possible to reduce the manufacturing cost by not coating. It is also excellent in susceptibility to disintegration after ingestion. Therefore, it is clear that the solid preparation of the present invention can be used and manufactured as a supplement, a health food, a nutritionally functional food, a food with a functional claim, a food for specified health use, a pharmaceutical product, and the like, and is useful.

Claims (7)

It is a solid product to be taken orally.
With a gelling agent
Contains one or more selected from monosaccharides, disaccharides and oligosaccharides,
The solid preparation has a gelling agent and one or more selected from monosaccharides, disaccharides and oligosaccharides on the outermost surface.
Solid formulations (excluding (a) and (b) described below, which are designed to increase the lubricity of the surface by contact with an aqueous solution.
(A) A pharmaceutical composition in the form of a chewable skrullfate-containing tablet or sugar-coated tablet, which comprises at least one physiologically acceptable gel-forming agent.
(A) The following components (a), (b), (c) and (d):
(A) A drug having therapeutic activity;
(B) A gelling agent composed of a heteropolysaccharide gum and a homopolysaccharide gum that can be crosslinked with each other when in contact with an environmental liquid, and the ratio of the heteropolysaccharide gum to the homopolysaccharide gum is 1: 3 to 3: The gelling agent which is 1.
(C) A pharmaceutically acceptable sugar, a polyhydric alcohol, an industrially produced direct tableting diluent, and an inert diluent selected from the group consisting of mixtures thereof; and
(D) Contains a pharmaceutically acceptable hydrophobic substance,
The ratio of the inert diluent according to (c) to the gelling agent according to (b) is 1: 8 to 8: 1.
A release-controlled solid-state oral drug used to treat a disease in a patient suffering from the disease). The solid preparation according to claim 1, wherein the solid preparation is a tablet having a naked tablet. The solid preparation according to claim 1 or 2, wherein the gelling agent is contained in the central portion in addition to the outermost surface portion. The solid preparation according to any one of claims 1 to 3, wherein the central portion has at least one selected from monosaccharides, disaccharides and oligosaccharides in addition to the outermost surface portion. The solid preparation is characterized in that the gelling agent and one or more selected from monosaccharides, disaccharides and oligosaccharides are uniformly mixed.
The solid preparation according to any one of claims 1 to 4. With a gelling agent
It is a mixed powder tablet containing one or more selected from monosaccharides, disaccharides and oligosaccharides.
The solid preparation according to any one of claims 1 to 5. The solid preparation according to any one of claims 1 to 6, which is a naked tablet.

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