KR102329377B1 - solid formulation - Google Patents

Abstract

The solid preparation of the present invention is a solid preparation for oral ingestion, and is made so that the lubricity of the surface increases by contact with an aqueous solution. The solid preparation contains a gelling agent. In a solid preparation, the gelling agent is not gelled in the state before taking, and the gelling agent is gelled by contact with an aqueous solution at the time of administration. A solid preparation can be made into the form of a tablet or a capsule. The solid preparation preferably has a disintegration time of 60 minutes or less, measured using water as a solvent. It is preferable that the maximum stress measured by the predetermined method is lower than the maximum stress similarly measured for the solid preparation before it is put into water.

Description

solid formulation

The present invention relates to solid formulations.

With the recent rise in consumer health-consciousness and the introduction of the functional label food system as a new system for food labeling, it is expected that the Japanese health food supplement market scale will continue to expand in the future. Among supplements, solid preparations such as tablets are often used as preparations for oral administration. However, taking a large tablet or multiple tablets at the same time is difficult for those who are not good at swallowing tablets, especially children or the elderly with low swallowing function. many.

In order to make the tablet easy to swallow, it is required to improve the ease of slipping of the tablet, the difficulty in getting caught in the throat, and the like. In consideration of this point, a plurality of techniques for studying the coating of solid preparations such as tablets have been reported to date (Patent Documents 1 to 3). However, the coating makes the tablet surface slippery, and even if the dosage is improved to some extent, the resistance when passing through the pharynx having a complicated shape is still large, and the effect of improving swallowing is not sufficient.

Japanese Patent Laid-Open No. 11-60472 US2010/0266687A1 US2014/0294958A1

An object of the present invention is to provide a solid preparation that has little resistance and can be easily taken even by a person who is not good at swallowing the solid preparation.

The present invention is a solid preparation for oral ingestion,

To provide a solid preparation, which is configured to increase the lubricity of the surface by contact with an aqueous liquid.

BRIEF DESCRIPTION OF THE DRAWINGS It is a conceptual diagram of the measuring method of a maximum stress.
Fig. 2 is an electromyogram when only water is taken.
3 is an electromyogram when the tablet prepared in Example 1 is taken.
4 is an electromyogram when the tablet prepared in Example 2 is taken.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated based on the preferable embodiment.

The solid preparation of this embodiment is a solid preparation ingested orally, Comprising: The lubricity of the surface is comprised so that contact with an aqueous liquid may increase. The aqueous liquid here refers to a liquid, saliva, or a mixture thereof, which is normally used for drinking, such as water, tea, soft drink, and milk. Since the solid preparation of the present invention contains a gelling agent, surface lubricity is increased by contact with an aqueous solution. It is preferable that the solid preparation contains the gelling agent on the surface part. In the solid preparation of the present embodiment, the gelling agent is not gelled in the state before taking, and the gelling agent is gelled by contact with the aqueous solution at the time of taking. As the gelling agent, a substance that exhibits slippery properties when immersed in an aqueous solution in a powdery (particulate) form is used. In the present specification, gelation does not necessarily mean that the presence of a gel can be confirmed, and when the gelling agent comes into contact with an aqueous solution, slipperiness may be exhibited. However, it is preferable that the presence of the gel can actually be confirmed by contact with the aqueous solution. Specifically, the solid preparation is left standing on a plastic substrate, and 0.2 µL of water at 25°C is dripped with a dropper per 1 mm 2 of the surface area of the solid preparation, and then held in that state for 10 to 20 seconds , it is preferable that the presence of the gel can be confirmed.

The reason that the gelling agent exhibits slippery properties by contact with the aqueous liquid is that the maximum stress after the solid preparation of the present embodiment is poured into water is lower than the maximum stress before the solid preparation is put into water. can be confirmed by Here, to put in water means that the solid preparation is left standing on a plastic substrate, and 0.2 µL of water at 25°C is added dropwise with a dropper per 1 mm 2 of the surface area of the solid preparation, and the state is held for 10 to 20 seconds. it means. The procedure for measuring the maximum stress is as follows. A schematic diagram of the measuring device is shown in FIG. 1 . In FIG. 1, the code|symbol 1 is a solid preparation, the code|symbol 2 is a slit, and the code|symbol 3 is a silicone tube.

<Measurement procedure for maximum stress>

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 while the silicone tube is sandwiched in the left-right direction are used, and the silicone tube is located below the slit. , The maximum stress when one tablet is filled with a solid preparation and the silicone tube is moved upwardly with respect to the solid preparation by 20 mm at a speed of 0.5 mm/sec by moving the silicone tube upward along the slit is measured. In addition, as a silicone tube used for the said measurement, the cross-sectional area of a silicone tube is smaller than the cross-sectional area of a solid preparation, and the thing larger than 40% of the cross-sectional area of a solid preparation is used. The ratio of the cross-sectional area of the solid preparation to the cross-sectional area of the silicone 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 the solid preparation measured in the above procedure is added to water is preferably less than 20 N, more preferably 15 N or less, still more preferably 10 N or less, and 5 N or less. It is particularly preferred.

Said up-down direction is a direction orthogonal to a horizontal surface. In addition, said left-right direction means the direction orthogonal to an up-down direction.

The cross-sectional area of said silicone tube refers to the area of the part enclosed by the silicone tube inner surface in the cross section which cut|disconnected the silicone tube in the state which is not filled with a solid preparation in the direction orthogonal to the longitudinal direction.

In addition, the cross-sectional area of a solid preparation refers to the area of the cross section which has the largest area among the cross sections cut|disconnected by the plane orthogonal to the longitudinal direction of the silicone tube of the solid preparation in the state filled with a silicone tube.

Moreover, the disintegration time of the solid preparation of this embodiment measured using water as a solvent is less than 60 minutes, it is preferable that it is less than 40 minutes, and it is more preferable that it is less than 20 minutes. As a lower limit of disintegration time, 1 minute or more is mentioned, for example from manufacture easiness of a solid preparation. The disintegration time means the time until the sample in the solvent disintegrates. The procedure for measuring the disintegration time is in accordance with the method described in "Disintegration Test Method" of item "6.09" in the 15th revision Japanese Pharmacopoeia. When using tablets 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, it is preferable to use a disintegration tester made by Toyama Industrial Co., Ltd., model number: NT-400. It is preferable that the disintegration time with respect to the agent thickness of the solid preparation of this embodiment is 0.01 min/mm or more and 25 min/mm or less, It is more preferable that they are 0.05 min/mm or more and 20 min/mm or less, 0.1 min/mm or more It is more preferably 12 min/mm or less, more preferably 0.15 min/mm or more and 8 min/mm or less, and most preferably 0.2 min/mm or more and 4 min/mm or less.

<Measurement procedure for decay time>

In each of the glass tubes of the disintegration tester having six glass tubes, one tablet of the solid preparation is placed. The upper and lower surfaces of each glass tube are opened, and the stainless steel mesh|network of the spacing of 1.8 mm - 2.2 mm of meshes is attached to the lower surface of the glass tube. The glass tube into which the solid preparation was put was put in 37±2 degreeC water, and the disintegration tester was operated. The glass tube in the disintegration tester is observed, and when it is confirmed that the solid preparation is starting to disintegrate, the glass tube is pulled up and the state of the disintegration of the solid preparation is observed. Repeat this operation, observing until the solid formulation completely disintegrates. The time from when the disintegration tester was operated until the disintegration of all six solid formulations was measured, and the measured time was taken as the disintegration time. In addition, when the residue of the solid preparation is not confirmed at all in the glass tube, or is a soft substance that does not leave a clear shape even if it is confirmed, the solid preparation is considered to be disintegrated.

As a form of the solid preparation of this embodiment, a tablet, a capsule, a pill, a powder, etc. are mentioned, It is preferable to set it as the form of a tablet or a capsule. In any form, the gelling agent is present on the outermost surface of the solid preparation. The outermost 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 direction. It is especially preferable that the solid preparation of this embodiment has a gelling agent in the whole outermost surface part. In this specification, if it can be confirmed that a gelling agent exists in two or more different points in the outermost surface part of a solid formulation, it can be said that it has a gelling agent in the whole outermost surface part. Here, the presence of the gelling agent in the surface portion can be confirmed by scraping off about 30 mg of an arbitrary point of 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 tableting product of a mixed powder containing a gelling agent.

The solid preparation may have a structure in which the surface part and the part on the center side were distinguished from it, or does not need to have such a structure. For example, the solid preparation may have a multilayer structure such as a core-coated tablet. Especially, when a solid preparation does not have a multiple layer structure and it is a single layer structure, it is preferable from points, such as manufacturing easiness.

The solid preparation may have a gelling agent in points other than the outermost surface part. For example, the solid preparation may contain the gelling agent in both the outermost surface part and the part on the central side (it is also called a central part) from it. Examples of such a solid preparation include tablets having uncoated tablets of a single layer structure. In the solid preparation, the composition of the outermost portion and the composition of the central portion may be the same or different. The presence of a gelling agent in the center of the solid preparation means, for example, that the solid preparation is cut in half with a cutter or the like, and about 30 mg of any point in the central portion of the solid preparation is greater than 1 mm from the surface of the solid preparation with a scalpel. It can be confirmed by scraping off with a rag, adding an appropriate amount of a liquid medium, such as water, to form a gel. In addition, the component listed as a disintegrant mentioned later is not contained in the gelatinizer in this application.

The case where the solid preparation of this embodiment is a tablet is demonstrated.

The tablet is preferably a tablet having an uncoated tablet having a gelling agent. In general, uncoated tablets (also referred to as “predetermined tablets”) refer to tablets in which a coating layer is not formed on the surface. As used herein, the term "tablet having an uncoated tablet" means a tablet in which a coating layer is not formed on the surface of the tablet, and the portion is in a state of uncoated tablets (hereinafter referred to as a tablet in which a coating layer on the surface of the tablet is not formed). The part is called the naked part). In addition, in this specification, "uncoated tablet" means a tablet in which the coating layer is not substantially formed on the surface (tablet whose ratio of the area covered by the coating layer to the surface area of a tablet is less than 5%). In the present specification, "uncooked tablet" is a concept included in "tablets having uncoated tablets."

The tablet having an uncoated tablet of the present embodiment exhibits a slippery property (also referred to as slipping property) when a liquid medium such as water comes into contact with the uncoated tablet portion. It is preferable that the tablet which has an uncoated tablet of this embodiment has a gelling agent in the outermost surface part of a raw tablet part. The outermost surface portion refers to a portion located on the surface side in the bare tip portion, and refers to a range of 0 mm or more and 1 mm or less from the surface of the bare tip portion toward the center direction. The tablet of the present embodiment has a gelling agent on the outermost surface of the uncoated portion, particularly the uncoated portion, so that when it comes into contact with a liquid medium such as water, slipperiness is generated on the surface of the uncoated portion. As a result, the tablet having an uncoated tablet of the present embodiment is easily swallowed even without forming a coating layer. It is particularly preferable that the tablet having an uncoated tablet has a gelling agent over the entire outermost surface portion of the uncoated tablet portion. In the present specification, if it can be confirmed that the gelling agent is present at two or more different points in the outermost surface portion of the bare crystal portion, it can be said that the gelling agent is present in the entire outermost surface portion of the bare crystal portion. The presence of a gelling agent in the surface portion can be confirmed by scraping off about 30 mg of an arbitrary point 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 an uncoated tablet having a gelling agent on the entire outermost surface of the uncoated tablet portion can be easily obtained as a tableting product of a mixed powder containing a gelling agent.

Since the effect of a gelling agent is exhibited by the presence of an uncrystal part in the tablet which has said uncoated tablet, it is preferable that a raw-crystal part exists in the outermost surface of a tablet. Specifically, the ratio of the surface area occupied by the bare crystal portion on the outermost surface of the tablet is preferably 70% or more, more preferably 90% or more, and particularly preferably 95% or more. In addition, when the above-mentioned uncoated tablet having a coating layer has a coating layer, the ratio covered by the coating layer to the surface area of the tablet is preferably less than 30%, particularly preferably less than 10%, and is substantially free of a coating layer (surface area of the tablet) It means that the ratio of the area covered by the coating layer occupied by is less than 5%) is most preferable. Further, when the tablet having the above-mentioned uncoated 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 making the thickness of a coating layer into 1 mm or less, while making it easy to exhibit the effect of a gelling agent, while being able to reduce manufacturing cost, enlargement of a tablet can be prevented. In the case where the coating layer covers only a part of the tablet, the coating layer may be present continuously while being biased toward a part, or may be dispersed in the form of an island or the like. For example, if a coating layer is present on a part of the surface of the tablet by burying a powdery material other than a gelling agent (for example, saccharides or other seasonings, etc.) on the surface of the uncoated tablet, Because it works, it can be tolerated.

When the solid preparation of this embodiment is a capsule, it is preferable that the capsule is coat|covered with the coating layer containing a gelling agent. It is preferable that the gelling agent adheres to the surface of a capsule film. For example, by mixing a powder containing a gelling agent with a soft capsule (soft capsule) or hard capsule (hard capsule), the surface of the capsule can be coated with a coating layer. At this time, the adhesion may be improved by wetting the surface of the capsule with a solvent or the like. When the powder containing the gelling agent does not easily adhere to the surface of the soft capsule or hard capsule, the adhesion of the powder can be improved by wetting the surface of the capsule. As another coating method, the surface of the capsule can be coated by spraying the solution which melt|dissolved the gelatinizer with respect to the soft capsule or hard capsule. Although a hard capsule may be sufficient as a capsule, a soft capsule is especially preferable. The range in which the surface of the capsule is covered with the coating layer is preferably 50% or more of the capsule surface area, more preferably 70% or more, still more preferably 90% or more, and most preferably the entire surface is covered.

When the solid preparation of this embodiment is a pill, it is preferable that the pill has a leprosy containing a gelling agent. Such leprosy exhibits slippery properties when the surface comes into contact with water. In general, leprosy refers to a pill that does not have a coating layer formed on its surface. The pill has a gelling agent on the outermost surface of the leprosy, especially in the leprosy, so that the surface of the leprosy is slippery when it comes into contact with a liquid medium such as water. In this way, the pill is easily swallowed even without forming a coating layer. Since the pill, which is a leprosy, does not form a coating layer covering the entire surface thereof, there is an advantage in that the enlargement of the pill can be prevented and the manufacturing cost can be reduced.

When the solid preparation of this embodiment is a powder, it is preferable that the powder is coat|covered with the coating layer containing a gelling agent. For example, by spraying a solution containing a gelling agent onto the powder used as a core material, a powder whose surface is partially covered with a coating layer containing a gelling agent can be obtained.

In order to realize the above slippery properties and disintegration time, preferred components and compositions used in the solid preparation of the present embodiment will be described in detail below.

The components and compositions of the following solid preparations 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 an uncoated tablet, and the components and compositions of the following solid preparation correspond to the components and compositions contained in the uncoated tablet constituting the tablet.

A gelling agent is mix|blended with a solid formulation for the purpose of surface lubricity increasing by contacting with an aqueous liquid. As the gelling agent contained in the solid preparation, a substance exhibiting slippery properties when immersed in a liquid medium such as water in the form of a powder (particulate) is used. Gelling agents include, for example, xanthan gum, locust bean gum, guar gum, mannan, glucomannan, hyaluronic acid, agar, alginic acid, tamarind gum, psyllium seed gum, tara gum, carrageenan, acacia gum, gum arabic, Gum garty, gum tragacanth, karaya gum, cassia gum, ramzan gum, welan gum, macrophomopsis gum, curdlan, pullulan, gellan gum (deacylated gellan gum, native gellan gum), pectin, and natural polysaccharides such as soybean polysaccharides; protein degradation products such as collagen; polyamino acids such as polyglutamic acid; and at least one selected from biopolymers such as polylactic acid and polyglutamic acid, and salts and derivatives thereof. Among them, natural polysaccharides are particularly preferable.

As said derivative, a hyaluronic acid derivative, an alginic acid derivative, a polyglutamic acid derivative, etc. are mentioned. Moreover, as said salt, alginate, hyaluronate, polyglutamate, etc. are mentioned. Examples of the hyaluronic acid derivative include hyaluronic acid esters and acetylated hyaluronic acid. Alginic acid ester etc. are mentioned as an alginic acid derivative. Polyglutamic acid ester etc. are mentioned as a polyglutamic acid derivative. Examples of the alginate include sodium alginate, potassium alginate, ammonium alginate and calcium alginate. Examples of the hyaluronate include sodium hyaluronate and potassium hyaluronate. As polyglutamate, sodium polyglutamate, potassium polyglutamate, etc. are mentioned. A gelling agent may be used individually by 1 type, and may be used in combination of 2 or more type.

Gelling agent, locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, gum arabic, garty gum, tragacanth gum, karaya gum, cassia gum, ramzan Gum, welan gum, macrophomopsis gum, curdlan, pullulan, gellan gum, polyamino acids, polylactic acid, and at least one selected from salts and derivatives thereof (hereinafter also referred to as specific gelling agents) containing It is preferable because it is easy to disintegrate in the body after ingestion, and in particular, it is preferable that containing locust bean gum is excellent in disintegration after ingestion, and coexistence of disintegration property and slippery property is exhibited at a high level.

In addition, combining two or more types of gelling agents is also preferable from the viewpoint of achieving both disintegration properties and slippery properties and from the viewpoint of manufacturability, and it is more preferable to combine a specific gelling agent with a gelling agent other than the specific gelling agent. Specifically, it is preferable to combine locust bean gum, which is a specific gelling agent, and xanthan gum, guar gum, alginic acid, carrageenan, or the like, 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 a slippery feeling can be effectively increased. Furthermore, by combining locust bean gum with guar gum, a solid preparation excellent in disintegration properties in the body after ingestion can be obtained.

Among the solid preparations, the proportion of the gelling agent is preferably 0.01 mass% or more, in order to sufficiently generate a slippery feeling when in contact with a liquid medium such as water. Moreover, it is preferable that the ratio of the gelling agent in a solid preparation is 70 mass % or less from points, such as the easiness of dissolution of an active ingredient. From these points, in the solid formulation, the proportion of the gelling agent is more preferably 0.1 mass% or more and 60 mass% or less, still more preferably 1 mass% or more and 50 mass% or less, and still more preferably 3 mass% or more and 30 mass% or less. It is preferable, and it is most preferable that it is 5 mass % or more and 20 mass % or less. When the solid formulation of the present embodiment contains at least one selected from the above specific gelling agents in the solid formulation, as a preferable range of the total mass of the specific gelling agent in the solid formulation, the preferred range of the above-mentioned gelling agent; The same range can be mentioned. As used herein, the total mass of at least one type selected from the specific gelling agent is the mass of one type when the solid formulation contains only one type selected from the specific gelling agent, and the solid formulation is two or more types of these. If they are included, it is their total mass.

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, from the viewpoint of coexistence of slipperiness and disintegration properties, the former with respect to 100 parts by mass of the latter. It is preferable that they are 10 mass parts or more and 1000 mass parts or less, It is more preferable that they are 15 mass parts or more and 900 mass parts or less, It is especially preferable that they are 20 mass parts or more and 800 mass parts 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 is 100 parts by mass of xanthan gum from the viewpoint of increasing the slipperiness and content of the active ingredient. On the other hand, it is still more preferable that locust bean gum is 10 mass parts or more and 1000 mass parts or less, It is still more preferable that they are 15 mass parts or more and 900 mass parts or less, It is especially preferable that they are 20 mass parts or more and 800 mass parts or less.

In addition, 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 slipperiness and content of the active ingredient, with respect to 100 parts by mass of guar gum, locust bean gum It is still more preferable that they are 10 mass parts or more and 1000 mass parts or less, It is still more preferable that they are 15 mass parts or more and 900 mass parts or less, It is especially preferable that they are 20 mass parts or more and 800 mass parts or less.

The solid preparation preferably further contains at least one selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch decomposition products (hereinafter these are also referred to as specific excipients). By combining the gelling agent and these specific excipients, a solid formulation having excellent slipperiness and a short disintegration time is obtained.

Specific excipients include, as described above, (A) monosaccharides, (B) disaccharides, (C) oligosaccharides, (D) cellulose, (E) cellulose derivatives, (F) starch, (G) starch derivatives, and (H) ) It may contain at least one selected from starch decomposition products, but from the viewpoint of achieving both disintegration properties and slippery properties, among the components described in (A) to (H), two or more components belonging to different categories are included in combination it is preferable Specific examples thereof include a combination of disaccharide and cellulose, a combination of disaccharide and reduced maltose, and a combination of disaccharide and starch. Moreover, it is further more preferable to contain the component which belongs to a different division among the components described in (A)-(H) in combination. Specific examples thereof include a combination of disaccharides, starch and cellulose, a combination of disaccharides, reduced maltose, and cellulose, and the like.

Examples of the sugar alcohol include monosaccharide alcohol, disaccharide alcohol, and trisaccharide or higher alcohol. Examples of the monosaccharide alcohol include tetritol such as erythritol, D-threitol and L-threitol, pentitol such as D-arabinitol and xylitol, D-iditol, and galactitol (dulcitol); Hexitol, such as D-glucitol (sorbitol), cyclitol, such as inositol, mannitol, bolemitol, ribitol, perceitol, D-erythro-D-galacto-octitol, etc. are mentioned. Moreover, as an alcohol of a disaccharide, reduced maltose (maltitol), lactitol, reduced palatinose (isomalt), etc. are mentioned, for example. Moreover, as a trisaccharide or more alcohol, maltotriitol, isomaltotriitol, panitol, etc. are mentioned. The sugar alcohol is preferably at least one selected from disaccharide alcohols in particular from the viewpoint of manufacturability such as obtaining the hardness of a particularly tableted tablet by combination with the gelling agent used in the present invention. It is preferable that it is at least 1 sort(s) selected from maltose and reduced palatinose.

Examples of monosaccharides include glucose, galactose, fructose, and mannose. Among these, glucose is preferred from the viewpoint of achieving both availability and disintegration properties and slippery properties.

Examples of the disaccharide include sucrose, maltose, lactose (lactose), trehalose, turanose, and cellobiose. Among these, at least one selected from trehalose, sucrose and maltose is preferable from the viewpoint of disintegration, and sucrose and maltose are more preferable from the viewpoint of achieving both ease of availability and disintegration property and slippery property. Although the effects of the present invention can be obtained even when lactose is included, the disaccharide is more preferably a disaccharide other than lactose from the viewpoint of achieving both disintegration properties and slippery properties.

Examples of the oligosaccharide include trisaccharides or more and twenty sugars or less, preferably three sugars or more and ten sugars or less, more preferably three or more hexasaccharides or less, and specifically, raffinose, maltotriose, melezitose, Gentianose, acarbose, stachyose, galactooligosaccharide, fructooligosaccharide, mannan oligosaccharide, isomaltooligosaccharide (isomaltotriose, panose), xylooligosaccharide, soybean oligosaccharide, nigero oligosaccharide, milk oligosaccharide can be heard In particular, it is preferable to use isomaltooligosaccharide or fructooligosaccharide from the viewpoint of achieving both ease of availability and disintegration properties and slippery properties.

It is preferable that the solid preparation contains any of monosaccharides, disaccharides, and oligosaccharides, not only in terms of taste masking but also in terms of promoting secretion of saliva. In particular, it is preferable that the solid preparation contains these saccharides on the surface portion.

Examples of the cellulose include powdered cellulose and crystalline cellulose. Crystalline cellulose is a product obtained by partially depolymerizing α-cellulose obtained as pulp from a fibrous plant with an acid and refining it. For example, those corresponding to the crystalline cellulose described in the 15th revision Japanese Pharmacopoeia Explanatory Manual (published by Hirogawa Bookstore) are mentioned. Crystalline cellulose can be classified into a crystalline cellulose powder and a crystalline cellulose composite, and both 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 preferably has a degree of etherification of 0.2 mol/C6 to 1.0 mol/C6 in terms of availability and coexistence of slipperiness and disintegration time, and more preferably 0.5 mol/C6 to 0.8 mol/C6. desirable. Although the effects of the present invention are obtained even when croscarmellose sodium or low-substituted hydroxypropyl cellulose is internally crosslinked with sodium carboxymethylcellulose, from the viewpoint of achieving both disintegration and slippery properties, a cellulose derivative is used. It is more preferable that they are cellulose derivatives other than croscarmellose sodium and low-substituted hydroxypropyl cellulose.

Examples of the starch include natural starch. Examples of the origin of starch include corn, potato, arrowroot, tapioca, sweet potato, rice, barley, wheat, barley, yam, and taro sweet potato. When blending starch, in particular, blending in combination with sugar alcohol is preferable from the viewpoint of achieving coexistence of disintegration properties and slippery properties.

Examples of starch derivatives include chemical starch, oxidized starch, enzyme-treated starch, α-starch, phosphate starch, distarch phosphate, starch acetate, octenylsuccinate starch, glycerol distarch, carboxymethyl starch, hydroxypropyl starch, crosslinked starch, and soluble starch, grafted starch, and sodium carboxymethyl starch, and α-starch is preferable from the viewpoint of coexistence of slipperiness and disintegration time. When blending a starch derivative, it is particularly preferable to blend in combination with a sugar alcohol from the viewpoint of achieving both disintegration properties and slippery properties. In addition, although the effect of the present invention is obtained even when sodium carboxymethyl starch is included, from the viewpoint of achieving both disintegration properties and slippery properties, the starch derivative is more preferably a starch derivative other than sodium carboxymethyl starch. do.

As a starch decomposition product, dextrin is mentioned, The thing of DE of 8-9.5 is mentioned preferably.

It is preferable that 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 raw tablet, from the viewpoint of further enhancing the effect of using the gelling agent and the specific excipient in combination, and 100 parts by mass of the gelling agent in the raw tablet. It is preferable that the quantity of a specific excipient|filler is 3000 mass parts or less with respect to mass part at the point which raises content of an active ingredient. From these points, with respect to 100 parts by mass of the gelling agent in the solid formulation, the amount of the specific excipient in the solid formulation is preferably 10 parts by mass or more and 3000 parts by mass or less, more preferably 20 parts by mass or more and 2500 parts by mass or less, and 30 parts by mass It is especially preferable that it is more than part and 2000 mass parts or less.

In addition, with respect to 100 parts by mass of the solid preparation, 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 and 70 parts by mass or less. It is also preferable that it is less than part. In particular, in terms of disintegration properties, the specific excipient preferably accounts for 40 mass% or more in the solid formulation, more preferably 50 mass% or more, still more preferably 60 mass% or more, and may be 70 mass% or more. Moreover, as an upper limit of the amount of a specific excipient, it is preferable that it is 95 mass % or less in a solid formulation from the point containing a gelling agent, and it is more preferable that it is 90 mass % or less.

Among specific excipients, the solid preparation in the present invention preferably contains at least one selected from monosaccharides, disaccharides, oligosaccharides, starch derivatives (especially α-starch) and starch decomposition products, from the viewpoint of high slippery properties, , more preferably containing monosaccharides, disaccharides, oligosaccharides or starch decomposition products.

In particular, it is preferable that the solid preparation contains monosaccharides, disaccharides, oligosaccharides, sugar alcohols, crystalline cellulose or cellulose derivatives (especially carboxymethyl cellulose) as specific excipients from the viewpoint of excellent disintegration properties in addition to slippery properties, monosaccharides, disaccharides, It is more preferable to contain an oligosaccharide, a sugar alcohol or carboxymethyl cellulose.

In addition, containing sugar alcohols and disaccharides enhances the binding property of the raw powder of the solid preparation, and when the solid preparation is a tablet, ease of manufacture of the preparation, such as obtaining the hardness of a tableted tablet, and unpleasant taste of the active ingredient It is also preferable at the point from which a masking effect is acquired.

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

In addition, as a specific excipient, it is preferable from the viewpoint of improving disintegration property and slipperiness that the solid preparation contains a combination of disaccharides, and at least one selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch and starch decomposition products, In particular, a combination of a disaccharide with an oligosaccharide or a cellulose derivative is preferable. Uncoated tablet, as a specific excipient, when it contains a disaccharide in combination with another specific excipient, from the viewpoint of coexistence of slipperiness and disintegrability, the other specific excipient is 1 part by mass or more and 1000 parts by mass or less with respect to 100 parts by mass of the disaccharide It is more preferable that they are 5 mass parts or more and 300 mass parts or less, It is still more preferable, and it is especially preferable that they are 5 mass parts or more and 100 mass parts or less.

In addition, it is preferable that the solid preparation contains, as a specific excipient, a sugar alcohol and starch or α-starch in combination from the viewpoint of improving disintegration properties and slipperiness. When the solid preparation contains a sugar alcohol in combination with starch or α-starch as a specific excipient, from the viewpoint of coexistence of slipperiness and disintegration properties, 10 parts by mass of starch or α-starch per 100 parts by mass of the sugar alcohol It is more preferable that they are more than 1000 mass parts, It is more preferable that they are 30 mass parts or more and 700 mass parts or less, It is especially preferable that they are 50 mass parts or more and 500 mass parts or less.

In this embodiment, it contains starch, a starch derivative or a starch decomposition product, and combining this with xanthan gum, locust bean gum and guar gum, and salts and derivatives thereof, especially locust bean gum, has a good balance between hardness and gelation degree. It is preferable from the point of being easy to obtain a solid preparation with easy swallowing.

In addition, as will be described later, sugar alcohols are prepared from xanthan gum, locust bean gum and guar gum and salts and derivatives thereof under conditions that do not contain particles containing a gelling agent and a sugar alcohol whose surface is coated with a gelling agent. It is also preferable to combine with at least 1 type selected from the point which is excellent in hardness, easy swallowing, and slidability, and it is easy to obtain the easy swallowing solid preparation further. In addition, as will be described later, under conditions that do not contain a coating layer of the gelling agent, a gelling agent composed of at least one selected from starch, xanthan gum, locust bean gum or guar gum, and salts and derivatives thereof and reduced maltose It is also preferable that it is a solid preparation containing.

It is preferable that the solid preparation contains a specific excipient in the outermost portion, and in the case where the solid preparation is a tablet having an uncoated tablet, it is preferable that the specific excipient is also contained in the central portion.

<Other ingredients>

It is preferable that a solid preparation contains silicon dioxide etc. as a fluidity improving agent. As silicon dioxide, particulate silicon dioxide and light anhydrous silicic acid are mentioned. In the case of 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 1.8 parts by mass or less, further preferably with respect to 100 parts by mass of the solid formulation. is 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 a solid preparation contains a lubricant from the point of improvement of productivity (prevention of mortar adhesion at the time of tableting). As a lubricant, magnesium stearate and a calcium stearate are mentioned, for example. When it contains a lubricant, it is preferable in the solid formulation of this invention that they are 0.1 mass % or more and 20 mass % or less, and, as for the ratio, it is more preferable that they are 0.5 mass % or more and 10 mass % or less.

A solid preparation may contain an active ingredient. The active ingredient referred to herein may be a drug, or may be a functional ingredient other than a drug, or a processed product derived from plants, animals, or microorganisms. The solid preparation may contain, in addition to the above active ingredients, specific excipients, silicon dioxide, disintegrants, lubricants, and saccharides, a binder, seasonings other than saccharides, emulsifiers, fragrances, and the like. In addition, the solid preparation of this embodiment is oral, that is, internal use, and is a tablet for swallowing. It goes without saying that the solid preparation of the present embodiment may be used as a supplement, a health food, a nutritional functional food, a functionally labeled food, a food for specific health use, and a pharmaceutical.

The solid preparation of the present embodiment contains seasonings and/or fragrances other than saccharides on the outermost surface portion, thereby promoting the secretion of saliva when the solid preparation is held in the oral cavity, and supplying a liquid medium such as water to the solid preparation. can increase As said seasoning, a sweetener, an acidulant, etc. can be used. As the sweetener, a sucralose derivative of sucralose, peptide sweeteners such as aspartame, alitam, neotame and glycyrrhizin, stevia, licorice, and 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 a flavoring agent, in addition to citrus flavors, such as a grapefruit flavor, a lemon flavor, and an orange flavor, the flavor of fruit, etc. can be used.

The solid preparation according to the present embodiment may contain a disintegrant. Examples of the disintegrant include sodium bicarbonate (sodium bicarbonate), magnesium carbonate, carmellose calcium, sodium starch glycolate, etc., which can be used as food additives, crospovidone, sodium carboxymethyl starch, croscarmellose sodium , and low-substituted hydroxypropyl cellulose. Although the effect of the present invention is exhibited even when a disintegrant is included, from the viewpoint of excellent slipperiness, the content of the disintegrant is preferably small, and specifically, the blending amount of the disintegrant with respect to 100 parts by weight of the solid formulation 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, still more preferably 3 parts by weight or less, particularly preferably 1 part by weight or less, and most preferably not containing desirable.

Among the above disintegrants, one or more disintegrants selected from crospovidone, sodium carboxymethyl starch, croscarmellose sodium, or low-substituted hydroxypropyl cellulose from the viewpoint of excellent slipperiness (hereinafter these are also referred to as specific disintegrants) It is preferable that the content of ) 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 even more preferably 3 parts by weight or less with respect to 100 parts by weight of the solid formulation. Preferably, 1 part by weight or less is highly preferred, and none is most preferred. In addition, low-substituted hydroxypropyl cellulose is produced by reacting propylene oxide and alkali cellulose at high temperature, and drying at 105°C for 1 hour means containing 5.0 to 16.0% of hydroxypropyl groups.

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. Although the effect of the present invention is exhibited even when the surface contains particles containing the sugar alcohol and the gelling agent coated with the gelling agent, from the viewpoint of excellent disintegration property, the sugar alcohol and the gelling agent whose surface is coated with the gelling agent It is preferable that the content of the particles containing It is more preferably not more than 3 parts by weight, more preferably not more than 3 parts by weight, still more preferably not more than 1 part by weight, and most preferably no content. Particles containing the sugar alcohol and the gelling agent whose surface is coated with the gelling agent are formed by, for example, spraying the gelling agent onto the sugar alcohol-containing particles. In the present invention, the disintegration time is shortened by making the solid preparation not contain particles containing the gelling agent and the sugar alcohol whose surface is coated with the gelling agent, and the gelling agent and the specific excipient are uniformly mixed. it becomes easier to do

It can be confirmed, for example, by examining the distribution of the gelling agent in the solid preparation by cross-sectional imaging such as TOF-SIMS, that the surface is free of particles containing the sugar alcohol and the gelling agent coated with the gelling agent. 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 solid preparation, the solid preparation of the present invention contains a sugar alcohol whose surface is coated with the gelling agent and the gelling agent. It can be said that it does not contain the particle|grains containing.

As a solid preparation, in consideration of ease of swallowing, for example, in the case of a disc-shaped tablet, the weight of one tablet is preferably 100 mg or more and 500 mg or less, more preferably 120 mg or more and 450 mg or less, 150 mg or more and 400 mg or less is most preferred. 5 mm or more and 12 mm or less are preferable, as for a diameter, 5.5 mm or more and 11 mm or less are more preferable, 6 mm or more and 10 mm or less are the most preferable. 2 mm or more and 10 mm or less are preferable, as for thickness, 2.5 mm or more and 9 mm or less are more preferable, 3 mm or more and 8 mm or less are the most preferable. 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. A diameter, thickness, and hardness can be measured by the method mentioned later.

Hereinafter, the preferable manufacturing method of the solid preparation of this embodiment is demonstrated further.

The manufacturing method of this embodiment uses a raw material powder containing a gelling agent and at least one (specific excipient) selected from a sugar alcohol, monosaccharide, disaccharide, oligosaccharide, cellulose, cellulose derivative, starch, starch derivative, and starch decomposition product. It is desirable to prepare tablets, particularly tablets having uncoated tablets, 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, active ingredients, seasonings, fragrances, etc. listed above 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 gelling agent component, the preferable mass ratio of the specific excipient, and the preferable mass ratio of silicon dioxide, disintegrant, and lubricant are the above-mentioned solid It is the same as these preferable mass ratios in a formulation.

Moreover, as mentioned above, when a tablet is nucleated|nucleated, the raw material powder containing arbitrary nuclei as raw material powder is tableted.

The raw material powder containing the gelling agent and the specific excipient may be a mixture itself of the powdered gelling agent, the powdered specific excipient, and other powdered components included as necessary, or the powdered gelling agent and the powdered specific excipient The granulated powder obtained by granulating the mixture of other powdery components contained as needed may be sufficient.

As a granulation method, a well-known granulation method used when manufacturing an oral tablet by the granule tableting method can be used without limitation in particular.

A preferred method for producing the solid preparation of the present embodiment is preferably a powder of a gelling agent, and at least one powder selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, celluloses, cellulose derivatives, starches, starch derivatives and starch decomposition products. a step of mixing the mixture, 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 is compared to a solid preparation obtained by tableting particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent, a solid preparation in which the gelling agent is uniformly mixed with a specific excipient without such a coating layer, This is because, in particular, uncoated tablets are excellent in terms of disintegration properties and slippery properties, in particular, disintegration properties.

As described above, the solid preparation of the present embodiment is a tableted product of a mixed powder containing a gelling agent and a specific excipient, particularly a tableted product obtained by compressing the mixed powder obtained without spraying the mixed powder with an aqueous solution containing a gelling agent It is preferable because it is possible to easily obtain a solid preparation in which the gelling agent is present on the entire surface portion thereof. "A tableted product of a mixed powder containing a gelling agent and a specific excipient" and "A tableted product obtained by obtaining a mixed powder (including a gelling agent and a specific excipient) without spraying an aqueous solution containing a gelling agent, and tableting the mixed powder Even if the production method is included in the expression of circumstances existed.

The solid preparation of this embodiment is a solid preparation ingested orally, Comprising: The lubricity of the surface is comprised so that contact with an aqueous liquid may increase. In particular, as described above, when the solid preparation is a tablet having an uncoated tablet, the uncoated tablet contains a gelling agent as described above, and thus has a hard appearance that is the same as a tablet having an uncoated tablet that does not contain a gelling agent at the time of storage. When it comes into contact with a liquid medium such as water, its surface is gelled, and it has a slippery feeling, flexibility and elasticity, and is easy to swallow. In addition, when it comes into contact with a liquid medium such as water, the shape of the uncoated tablet portion is maintained, and dissolution of the active ingredient or the like present in the uncoated tablet portion in the oral cavity is suppressed. As described above, the solid preparation of the present embodiment has the characteristic of causing a feeling of slipperiness on the surface of the uncoated tablet by swelling with a liquid medium such as water.

As mentioned above, as a preferable aspect of the tablet of this invention, the following are mentioned, for example.

(1) a gelling agent;

A tablet having an uncoated tablet comprising at least one selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives, and starch decomposition products.

(2) The tablet according to (1), wherein the raw tablet contains at least one 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, gum acacia, gum arabic, gatti gum, tragacanth gum, karaya gum, cassia gum, ramzan gum, welan gum, macrophomopsis gum, curdlan, pullulan, gellan gum (deacylated gellan gum, native gellan gum), pectin, and polysaccharides such as soybean polysaccharides; Protein degradation products, such as gelatin and collagen; polyamino acids such as polyglutamic acid; The tablet according to (1) or (2), which is at least one selected from biopolymers such as polylactic acid and polyglutamic acid, and salts and derivatives thereof.

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

(5) The tablet of any one of (1) to (4), except that it contains crospovidone, sodium carboxymethyl starch, croscarmellose sodium or low-substituted hydroxypropyl cellulose.

(6) a gelling agent;

The tablet of any one of (1) to (5), which has an uncoated tablet comprising at least one selected from monosaccharides, disaccharides, oligosaccharides, α-starch and starch decomposition products.

(7) locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, gum arabic, garty gum, tragacanth gum, karaya gum, cassia gum, ramzan at least one selected from gum, welan gum, macrophomopsis gum, curdlan, pullulan, gellan gum, polyamino acids, polylactic acid, and salts and derivatives thereof;

The tablet of any one of (1) to (6), having an uncoated tablet comprising at least one selected from monosaccharides, disaccharides, oligosaccharides, α-starch and starch decomposition products.

(8) locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, gum arabic, garty gum, tragacanth gum, karaya gum, cassia gum, ramzan at least one selected from gum, welan gum, macrophomopsis gum, curdlan, pullulan, gellan gum, polyamino acids, polylactic acid, and salts and derivatives thereof;

At least one selected from xanthan gum, guar gum, alginic acid, and carrageenan;

The tablet of any one of (1) to (7), which has an uncoated tablet comprising at least one selected from monosaccharides, disaccharides, oligosaccharides, α-starch and starch decomposition products.

(9) a gelling agent;

disaccharides,

The tablet of any one of (1) to (8), having an uncoated tablet comprising at least one selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch, and starch decomposition products.

(10) a gelling agent;

sugar alcohols,

It contains at least one selected from starch and α-starch,

The tablet according to any one of (1) to (9), which does not contain a coating layer of a gelling agent.

Example

Hereinafter, the present invention will be described in more detail by way of Examples. However, the scope of the present invention is not limited to these examples. In addition, as a material described in Tables 1-3, each commercially available product was used. In particular, as the isomaltooligosaccharide, isomalt 900P manufactured by Showa Industrial Co., Ltd. was used. In addition, as crystalline cellulose, Nippon Paper Co., Ltd. product KC Frock W-400G was used. As carboxymethyl cellulose, carboxymethyl cellulose calcium having a degree of etherification of 0.5 to 0.7 mol/C6 was used. As the starch powder, Papilla 102 manufactured by Freund Industrial Co., Ltd. was used. As the α-ized starch, NON-GMO corn alpha-Y manufactured by Sanwa Starch Kogyo Co., Ltd. was used. As the dextrin, Max 1000 manufactured by Matsutani Chemical Industry Co., Ltd. was used.

1. Evaluation of slippery properties

[Example 1]

As raw material powder, according to the compounding ratio of Table 1, 400 grains of various raw materials (except calcium stearate) were mixed in a plastic bag, and then passed through a sieve, and calcium stearate was further added and mixed. This mixed powder was directly tableted with a rotary tableting machine (Kikusui, Ltd.) to obtain a disk-shaped uncoated tablet. The hardness of the obtained raw tablet was measured with a Schreiniger tablet hardness tester. Moreover, as a result of measuring the tablet diameter (diameter) and tablet thickness of the obtained raw tablet with a Digital Nogisu (Degimatic Caliper CD-15AX; Mitsutoyo), it was found that the hardness was 7.4 kgf, the tablet diameter was 10 mm, and the tablet thickness was 3.52 mm. Moreover, as a result of measuring the weight of the obtained raw tablet, it was 270 mg. In addition, hardness, tablet diameter, tablet thickness, and weight are average values of each measurement value of 3 tablets.

[Example 2]

According to the compounding ratio of Table 1, except having changed the compounding ratio of the raw material powder, it carried out similarly to Example 1, and obtained the uncoated tablet. As a result of performing the same measurement as in Example 1 about the obtained uncoated tablet, it was hardness 7.7 kgf, tablet diameter 10 mm, tablet thickness 3.50 mm, and weight 270 mg.

[Evaluation of Examples 1 and 2]

For the uncoated tablets obtained in Examples 1 and 2, the measurement of the neck muscle potential at the time of ingestion and the feeling of taking questionnaire were conducted in a single-blind crossover manner.

In addition, the slope glide time was measured to evaluate the ease of sliding of the tablet.

・How to take uncooked tablets

The subjects selected 6 healthy adults who were aware that they had difficulty swallowing tablets (male/female ratio of 2:4). As for the method of administration, first, 4 target raw tablets were held in the mouth, then 20 ml of 22°C water was held in the mouth, and the raw tablets were taken with water.

・Measurement of myoelectric potential

For the electromyography measurement, an electromyography (wireless electromyography measurement and analysis system "Lateo" manufactured by AM Science Co., Ltd.) was used. Although the measurement method followed the manual attached to the electromyography, it was specifically implemented as follows. The electromyography electrode was attached to the neck, and in order to purify the neck, the subject was given 20 ml of water in the same amount as when taking the uncoated tablet. Next, the muscle potential of the neck when 20 ml of water was taken was measured. Then, after holding 4 uncooked tablets in the mouth, the muscle potential of the neck when taken with 20 ml of water was measured for each test group. The amount of muscle activity was obtained from an integral value calculated based on the obtained muscle potential (unit volts (V)), and a relative value was obtained when the amount of muscle activity when only water was taken was taken as 100 (%). The relative value once per person was added up and the value divided by the number of persons was defined as the amount of muscle activity (%). In addition, in FIGS. 1-3, 1 Count is 1/200 second.

In addition, the measurement of each test group was performed with a break of about 5 minutes, and the order of taking the uncooked tablet was changed for each subject.

・Question

In terms of ease of slipping, the lowest evaluation (-3 points) is the case where the tablet is not slippery enough that it does not pass through the throat and is difficult to swallow, which occurs when the tablet is taken, and no friction on the throat is felt and there is no pinching in the throat. The case of slipperiness and easy swallowing was rated in 7 grades with the highest rating (3 points).

For stickiness, the lowest rating (-3 points) is the case where the tongue or pharynx is sticky enough to feel adhesion, and swallowing is difficult. It evaluated in 7 steps used as evaluation (3 points|pieces).

・Slope glide time

150 ml of water per minute was supplied from the upper part of the channel to an aluminum channel having a U-shaped cross-section (a straight line when viewed from the side, a channel length of 90 cm and a width of 1.2 cm) fixed at an angle of 30°. In this state, one uncoated tablet was slid and flowed 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, the average value of 5 times was computed, and it was set as the slope sliding time (sec).

Table 1 shows the amount of muscle activity (%) of the neck obtained by electromyography measurement, and typical electromyograms are shown in FIGS. 2 to 4 .

Table 1 shows the average value and the measurement result of the slope time (seconds) of 6 people with respect to the evaluation points obtained by the questionnaire. In addition, in Table 1, the unit of the composition of a bare crystal is a mass part.

As is clear from Table 1 and Figs. 2 to 4, the uncoated tablets of Examples 1 and 2, compared with the case where only water was taken, the amount of muscle activity in the neck was suppressed by an increase of about 1.5 times, and the strength when taking It is not necessary, it does not feel the swallowing stress easily, and it is an uncooked tablet that is easy to swallow. It turns out that, while feeling the ease of slipping even in the questionnaire, uncoated tablets do not stick to the tongue or pharynx and are easily swallowed.

Moreover, in the uncoated tablet which mix|blended crospovidone, sodium carboxymethyl starch, croscarmellose sodium or low-substituted hydroxypropyl cellulose, compared with Example 1 or 2, the ease of sliding and the difficulty of sticking fall.

In addition, comparing the sliding time of the slope, as shown in Table 1, Examples 1 and 2 also slide in 2 seconds or less, and since the raw tablet of the Example becomes slippery when in contact with water, it becomes easy to swallow. it can be seen that there is

Moreover, the slidability of the uncoated tablet which mix|blended crospovidone, sodium carboxymethyl starch, croscarmellose sodium, or low-substituted hydroxypropyl cellulose is lowered compared with Example 1 or 2.

From the above, in the case of an uncooked tablet containing a gelling agent and a specific excipient (sugar alcohol, α-starch), even a person who is not good at swallowing the tablet can take it easily with little resistance.

2. Evaluation of disintegrability

[Examples 3 to 6]

According to the blending ratio in Table 1 below, the hardness was set to 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 5.08 mm). An uncoated tablet was obtained in the same manner as in Example 1, except that the weight was changed to 300 mg.

The disintegration time was measured for the obtained uncoated tablet by the following method. A result is shown in Table 2.

Collapse time

The disintegration time was measured at n=6 using a disintegration tester (Toyama Industrial Co., Ltd., model number: NT-40H) by the method described in the "disintegration test method" of item "6.09" in the 15th revision Japanese Pharmacopoeia. In addition, 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 uncoated tablet containing a gelling agent and a specific disintegrant (sugar alcohol, cellulose, cellulose derivative, starch) had a short disintegration time. Moreover, even when a specific disintegrating agent (crospovidone) was mix|blended, compared with the case where it was not mix|blended, the disintegration time was only shortened by about 20%.

3. Assessment of slipperiness and disintegration time

[Examples 7 to 14, 16 to 21, Comparative Example 1]

According to the compounding ratio of Table 3 below, in the same manner as in Example 1, to obtain an uncoated tablet. The obtained raw tablets of Examples 7-14, 16-21, and Comparative Example 1 had the same hardness, tablet diameter, and tablet thickness as those of Examples 3-5, and had a weight of 300 mg.

[Example 15]

57.1 parts by mass of sorbitol and 30.0 parts by mass of maltose are put into a fluidized bed granulator (fluidized bed granulation drying/coating machine type: FD-LAB-1 type, Paurexa), a suspension of crystalline cellulose is sprayed, and then xanthan gum is further diluted with hot water Particle composition (sugar alcohol and gel whose surface is coated with a gelling agent) in which a coating layer of xanthan gum is formed on the surface of particles consisting of a mixed powder of sorbitol and maltose, granulated by spraying a suspension of 0.1% (w/v) particles containing a topical agent) were obtained.

After mixing 0.5 parts by mass of calcium stearate with the obtained particle composition, it is tableted using a rotary tabletting machine (Kikusui, Ltd.), and the hardness, tablet diameter, and tablet thickness are all about the same as those of Examples 3 to 5, and the uncoated tablet weighing 300 mg got The amounts of crystalline cellulose and xanthan gum in the raw tablet were those shown in Table 1.

About the uncoated tablet obtained in Examples 7-21 and Comparative Example 1, the disintegration time was measured by the method similar to Examples 3-6. A result is shown in Table 3.

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

<Measurement procedure for maximum stress>

The bare crystal was left still on a plastic substrate, and 0.2 µL of water at 25°C was added dropwise with a dropper per 1 mm 2 of the surface area of the bare crystal, and it was maintained in that state for 15 seconds.

A pair of silicone tubes having an inner diameter of 9 mm and an outer diameter of 11 mm that are arranged along the vertical direction so that the longitudinal direction coincides with the vertical direction and are fixed to be movable in the vertical direction, and a pair of fixed silicone tubes with the silicone tube inserted in the left and right directions. A slit was used, and under the slit in the silicone tube, one of the above-mentioned uncoated tablets (tablet diameter 9 mm) was filled. The maximum stress when the silicone tube was moved along the slit by 20 mm upwards with respect to the uncoated crystal at a speed of 0.5 mm/sec was measured using a creep meter (RE233005C) manufactured by Yamaden Corporation. The cross-sectional area of the silicone tube used for the measurement was 50% of the cross-sectional area of the bare crystal. When the stress exceeded 20, the measurement was finished at that point. As the silicone tube, a clear silicone square tube manufactured by Fuso Rubber Industries, Ltd. was used. As the 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 from each other was 2 mm.

The maximum stress was calculated|required as an average value of three runs.

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

As can be seen from the comparison of Examples 7 to 21 and Comparative Example 1 in Table 3, the uncoated tablet of Comparative Example 1 containing only a specific excipient and not containing a gelling agent contained a gelling agent and a specific excipient. In the bare crystals of Examples 7 to 21, the maximum stress is greatly reduced.

Moreover, from the results of Examples 7-14, it turns out that the maximum stress is especially low in the case of the uncoated tablet containing a monosaccharide, a disaccharide, an oligosaccharide, or a starch decomposition product among specific excipients.

Further, from the comparison of Examples 15 and 16, compared to the uncoated tablet obtained by tableting particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent, the uncoated tablet obtained by mixing a sugar alcohol with a gelling agent and tableting disintegrates. It can be seen that the time is shortened and the maximum stress is lowered.

In addition, compared to the uncoated tablet obtained by tableting particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent, the disintegration time of the uncoated tablet obtained by mixing a sugar alcohol with a gelling agent is shortened and the maximum stress is lowered. The tendency is confirmed not only when sorbitol is used as a sugar alcohol but also 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, in particular, the disintegration time is shortened and the maximum stress is lowered. Among them, it can be seen that locust bean gum is particularly excellent.

In the same manner as in Example 1, the following uncoated tablets (Formulations 1-41) were prepared. To some extent, it was excellent in slipperiness and disintegration properties. In particular, a combination of two or more gelling agents, a raw tablet containing at least one selected from monosaccharides, disaccharides, oligosaccharides, starch derivatives and starch decomposition products, and an uncoated tablet containing two or more components belonging to different categories among specific excipients in combination , and disaccharides, oligosaccharides, sugar alcohols, cellulose derivatives, starch, and undecomposed tablets in which at least one selected from decomposition products were combined, and were excellent in slipperiness and disintegration properties. Further, sucrose is embedded in the uncoated tablets prepared in Formulation Examples 1 to 41, and the ratio of the coating layer occupied to the surface area of the tablet is 20% or more and less than 30% (adjust the ratio by attaching sucrose using water) It was also excellent in the slippery property and disintegration property also for the tablet which has a single tablet. Similarly, the uncoated tablet prepared so that the ratio covered by the coating layer to the surface area of the tablet was 5% or more and less than 10% was excellent in slipperiness and disintegration properties.

Prescription Example 42

An internal liquid (95 mass% of saffron oil, 5 mass% of beeswax) is prepared, and the capsule film (weight before drying) contains 16.4 mass% of glycerol, 36.8 mass% of purified water, 43.3 mass% of gelatin, and 3.5 mass% of caramel pigment. ) was filled into a soft capsule. Encapsulation was carried out by casting the capsule coating liquid into a film, filling the inner liquid into a film, heat-sealing, and drying the molded soft capsule (300 mg per tablet). With respect to 1 soft capsule, the soft capsule and locust bean gum were mixed so that the weight of locust bean gum (powder) might be 5 mg, and locust bean gum was attached. By this step, a soft capsule having a gelling agent adhered to a part of the surface was obtained.

Industrial Applicability

The solid preparation of the present invention is easy to swallow, and since it is not necessary to coat the entire surface, enlargement due to coating can be avoided, and manufacturing cost can be reduced by not applying coating. Moreover, it is excellent also in the ease of disintegration after ingestion. Therefore, it is clear that the solid preparation of this invention can be used and manufactured as a supplement, a health food, a nutritional function food, a functional food food, a food for specific health use, a pharmaceutical, etc., and is useful.

Claims (9)

As a solid preparation for oral ingestion,
a gelling agent,
containing at least one selected from monosaccharides, disaccharides and oligosaccharides;
The solid preparation has a gelling agent and at least one selected from monosaccharides, disaccharides and oligosaccharides on the outermost surface,
A solid preparation configured to increase the lubricity of the surface by contact with an aqueous liquid. The method of claim 1,
A solid preparation, wherein the gelling agent is at least one selected from locust bean gum, xanthan gum, guar gum, alginic acid or a salt thereof, carrageenan, hyaluronic acid or a salt thereof, pullulan and agar. The method of claim 1,
A solid preparation, wherein the gelling agent is at least one selected from locust bean gum, xanthan gum, guar gum, alginic acid or a salt thereof, and carrageenan. The method of claim 1,
A solid preparation having at least one selected from monosaccharides, disaccharides and oligosaccharides in the center as well. The method of claim 1,
A solid preparation, which is a tabletting product of a mixed powder containing a gelling agent and at least one selected from monosaccharides, disaccharides and oligosaccharides. 3. The method according to claim 1 or 2,
In the solid preparation, the gelling agent is not gelled in the state before administration,
The said solid preparation is a solid preparation in which the said gelatinizer gels when it comes into contact with an aqueous liquid at the time of taking. 3. The method according to claim 1 or 2,
A solid preparation having a disintegration time of less than 60 minutes, measured using water as a solvent. 3. The method according to claim 1 or 2,
As a solid preparation for oral ingestion,
The solid preparation is left standing on a plastic substrate, and 0.2 µL of water at 25°C is added dropwise per 1 mm 2 of the surface area of the solid preparation with a dropper, and after holding in that state for 10 to 20 seconds, the following procedure A solid preparation in which the maximum stress to be measured is lower than the maximum stress measured in the same way for the solid preparation before it is added to water.
<Measurement procedure for maximum stress>
A silicone tube arranged along the up-down direction and fixed to be movable in the up-down direction, and a pair of slits fixed while the silicon tube is sandwiched in the left-right direction are used, and in the silicon tube, the lower side of the slit is used. , The maximum stress when one tablet of the above-mentioned solid preparation is filled and the silicone tube is moved upwardly with respect to the solid preparation by 20 mm at a speed of 0.5 mm/sec by moving the silicone tube upward along the slit is measured.
In the above measurement, a silicone 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. 3. The method according to claim 1 or 2,
The solid preparation is in the form of a tablet or capsule.

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