JP2022120168A - Solid preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solid preparation that can be taken easily with less reluctance even by people who dislike taking a solid preparation.

SOLUTION: A solid preparation is a solid preparation to be ingested, in a form of an uncoated tablet containing a gelling agent and one or more selected from among sugar alcohols, cellulose, cellulose derivatives, starch, starch derivatives and starch degradation products; and is configured such that surface lubricity increases by contact with aqueous liquid; excluding specific solid preparations as described in claim 1.

SELECTED DRAWING: Figure 1

COPYRIGHT: (C)2022,JPO&INPIT

Description

The present invention relates to solid formulations.

With the recent rise in health consciousness among consumers and the introduction of the Foods with Function Claims system as a new food labeling system, it is expected that the size of the market for health foods and supplements in Japan will continue to expand. be. Among supplements, solid formulations such as tablets are often used as formulations for oral administration. 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 stuck in the throat, and the like. In consideration of this point, several techniques have been reported so far in which coating of solid formulations such as tablets is devised (Patent Documents 1 to 3). However, even if the coating makes the surface of the tablet slippery and improves the swallowability to some extent, the resistance when passing through the pharynx, which has a complicated shape, is still large, and the effect of improving swallowing is not sufficient.

JP-A-11-60472 US2010/0266687A1 US2014/0294958A1

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

The present invention is an orally ingested solid preparation,
To provide a solid preparation whose surface lubricity is increased 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 manufactured in Example 1 was taken. FIG. 4 is an electromyogram when the tablet manufactured in Example 2 was taken.

The present invention will be described below based on its preferred embodiments.
The solid preparation of the present embodiment is a solid preparation to be orally ingested, and the lubricity of the surface is increased by contact with an aqueous liquid. The term "aqueous liquid" as used herein refers to liquids normally used for drinking, such as water, tea, soft drinks, and milk, saliva, or mixtures thereof. Since the solid preparation of the present invention contains a gelling agent, surface lubricity is increased by contact with an aqueous liquid. The solid preparation preferably contains a gelling agent on its surface. In the solid preparation of the present embodiment, the gelling agent is not gelled before administration, and the gelling agent is gelled upon contact with the aqueous liquid upon administration. As the gelling agent, a powdery (particulate) substance that exhibits sliminess when containing an aqueous liquid is used. In the present specification, gelation does not necessarily mean that the presence of gel can be confirmed, and it is sufficient that the gelling agent exhibits sliminess upon contact with the aqueous liquid. However, it is preferred that the presence of the gel can actually be confirmed by contact with the aqueous liquid. Specifically, a solid preparation is placed on a plastic substrate, and 0.2 μL of water at 25° C. is dropped with a dropper per 1 mm ² of surface area of the solid preparation. It is preferable to be able to confirm the presence of the gel.

The fact that the gelling agent comes into contact with an aqueous liquid to exhibit sliminess means that the solid preparation of the present embodiment is subject to the maximum stress after the solid preparation is put into water. It can be confirmed by being lower than the previous maximum stress. Here, putting into water means that the solid preparation is left standing on a plastic substrate, and 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 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 apparatus is shown in FIG. Reference numeral 1 in FIG. 1 is a solid preparation, reference numeral 2 is a slit, and reference numeral 3 is a silicon tube.

<Procedure for measuring 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 in a state in which the silicon tube is sandwiched in the horizontal direction, the silicon tube is provided below the slit. One tablet of the solid preparation was filled on the side, and the silicon tube was 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 silicone tube is preferably 40% or more and 60% or less, more preferably 45% or more and 55% or less.

Furthermore, the solid preparation of the present invention preferably has a maximum stress of less than 20 N, more preferably 15 N or less, and preferably 10 N or less after the solid preparation is placed in water measured by the above procedure. More preferably, it is particularly preferably 5N or less.

The vertical direction is a direction orthogonal to a horizontal plane. Moreover, the left-right direction refers to a direction orthogonal to the up-down direction.
The above-mentioned cross-sectional area of the silicon tube refers to the area of the portion surrounded by the inner surface of the silicon tube in a cross section obtained by cutting the silicon tube in a direction perpendicular to its longitudinal direction in a state in which no solid preparation is filled.
In addition, the cross-sectional area of the solid preparation refers to the area of the largest cross-section of the solid preparation filled in the silicon tube taken along a plane orthogonal to the longitudinal direction of the silicon tube.

In addition, the solid preparation of the present embodiment has a disintegration time measured using water as a solvent within 60 minutes, preferably within 40 minutes, and more preferably within 20 minutes. The lower limit of the disintegration time is, for example, 1 minute or longer in terms of ease of production of solid preparations. Disintegration time means the time it takes for a sample in a solvent to disintegrate. The procedure for measuring the disintegration time follows the method described in the Japanese Pharmacopoeia 15th Edition, item "6.09", "disintegration test method". 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 manufactured by Toyama Sangyo Co., Ltd., model number: NT-400. The solid preparation of the present embodiment preferably has a disintegration time with respect to the thickness of the agent of 0.01 min/mm or more and 25 min/mm or less, more preferably 0.05 min/mm or more and 20 min/mm or less. It is preferably 0.1 min/mm or more and 12 min/mm or less, even more preferably 0.15 min/mm or more and 8 min/mm or less, and 0.2 min/mm or more and 4 min. /mm or less.

<Procedure for measuring disintegration time>
A solid preparation is placed in each glass tube of a disintegration tester having 6 glass tubes. Each glass tube is open on the upper and lower surfaces, and a stainless steel mesh with mesh openings of 1.8 mm to 2.2 mm is attached to the lower surface of the glass tube. Place the glass tube containing the solid formulation in water at 37±2° C. and activate the disintegration tester. Observe the glass tube in the disintegration tester, and when it is confirmed that the solid preparation is about to disintegrate, pull up the glass tube and observe the state of disintegration of the solid preparation. Repeat this operation and observe until the solid preparation is completely disintegrated. The time from when the disintegration tester is activated to when all six solid preparations disintegrate is measured, and the measured time is taken as the disintegration time. The solid preparation is considered to be disintegrated when no residue of the solid preparation is found in the glass tube, or when it is a soft substance that clearly does not retain its original shape.

The form of the solid preparation of the present embodiment includes 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 preparation. 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 toward the center from the surface of the solid preparation. It is particularly preferred that the solid preparation of the present embodiment has a gelling agent over the entire outermost surface. 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 of the solid preparation, it can be said that the solid preparation has the gelling agent over the entire outermost surface. Here, the presence of a gelling agent on the surface can be confirmed by scraping off about 30 mg from an arbitrary portion of the outermost surface 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 over the entire outermost surface can be easily obtained as a tableted product of mixed powder containing the gelling agent.

The solid preparation may have a structure in which the surface portion and the portion closer to the center are distinguished from each other, or may not have such a structure. For example, a solid formulation may have a multi-layer structure such as a dry-coated tablet. Among them, when the solid preparation does not have a multi-layered structure but has a single-layered structure, it is preferable in terms of ease of production and the like.

A solid preparation may have a gelling agent at a location other than the outermost surface. For example, the solid preparation may contain a gelling agent in both the outermost surface portion and the central portion thereof (also referred to as the central portion). Examples of such solid preparations include tablets having a single-layered core tablet. In the solid preparation, the composition of the outermost surface portion and the composition of the central portion may be the same or different, but they are preferably the same from the standpoint of ease of production of a tablet having a core. The presence of a gelling agent in the center of a solid preparation can be obtained by, for example, cutting the solid preparation in half with a cutter or the like, and removing about 30 mg of an arbitrary portion of the portion more than 1 mm from the surface of the solid preparation on the center side with a scalpel or the like. It can be confirmed by scraping off and adding an appropriate amount of liquid medium such as water to gel. Components listed as disintegrants to be described later are not included in the gelling agent in the present application.

A case where the solid preparation of the present embodiment is a tablet will be described.
Preferably the tablet is a tablet having a core tablet with a gelling agent. Generally, a plain tablet (also referred to as an uncoated tablet) refers to a tablet without a coating layer formed on its surface. As used herein, the term "tablet having a bare tablet" means a tablet having a portion where no coating layer is formed on the surface of the tablet, and that portion is in the form of a bare tablet (hereinafter referred to as the tablet surface The part where the coating layer is not formed is called the bare tablet part). In the present specification, the term "plain tablet" means a tablet on which a coating layer is not substantially formed on the surface (a tablet having a surface area covered by the coating layer of less than 5% of the surface area of the tablet). do. In the present specification, the term "naked tablet" is a concept encompassed by "a tablet having a bare tablet".

The tablet having the core tablet of the present embodiment exhibits sliminess (also referred to as slipperiness) when a liquid medium such as water comes into contact with the core tablet portion. The tablet having the core tablet of the present embodiment preferably has a gelling agent on the outermost surface of the core tablet portion. The outermost surface portion refers to a portion located on the surface side of the bare tablet portion, and refers to a range of 0 mm or more and 1 mm or less from the surface of the bare tablet portion toward the center. Since the tablet of the present embodiment has a gelling agent in the bare tablet portion, particularly in the outermost surface portion of the bare tablet portion, the surface of the bare tablet portion becomes slimy when in contact with a liquid medium such as water. As a result, the tablet having the core tablet of the present embodiment can be easily swallowed without providing a coating layer. It is particularly preferred that a tablet having a core tablet has a gelling agent over the entire outermost surface of the core tablet portion. In the present specification, if the presence of a gelling agent can be confirmed at two or more different locations on the outermost surface of the core tablet portion, it can be said that the entire outermost surface portion of the core tablet portion has the gelling agent. Here, the presence of the gelling agent on the surface can be confirmed by scraping off about 30 mg of the outermost surface at any location with a scalpel or the like and adding an appropriate amount of liquid medium such as water to gel. As described later, a tablet having a core tablet having a gelling agent on the entire outermost surface of the core tablet portion can be easily obtained as a tableted product of mixed powder containing the gelling agent.

In the tablet having the above-mentioned bare tablet, the existence of the bare tablet portion exerts the effect of the gelling agent, so it is preferable that the bare tablet portion is present on the outermost surface of the tablet. Specifically, the ratio of the surface area occupied by the bare tablet portion on the outermost surface of the tablet is preferably 70% or more, more preferably 90% or more, and particularly preferably 95% or more. In addition, when the tablet having the above-mentioned plain tablet has a coating layer, the ratio of the surface area of the tablet covered by the coating layer is preferably less than 30%, particularly preferably less than 10%, substantially Most preferably, there is no coating layer on the tablet (meaning that the percentage of the surface area of the tablet covered by the coating layer is less than 5%). When the tablet having the above-mentioned 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 toward the center from the surface of the bare tablet portion. By setting the thickness of the coating layer to 1 mm or less, the effect of the gelling agent can be easily exhibited, the manufacturing cost can be reduced, and an increase in the size of the tablet can be prevented. When the coating layer covers only a part of the tablet, the coating layer may be partially unevenly distributed continuously, or may be dispersed in islands or the like. For example, by sprinkling powdery substances other than gelling agents (e.g., sugars or other seasonings) on the surface of the core tablet, if a coating layer exists on a part of the surface of the tablet, It is acceptable because it works with the gelling agents present.

When the solid preparation of this embodiment is a capsule, the capsule is preferably coated with a coating layer containing a gelling agent. The gelling agent is preferably adhered to the surface of the capsule shell. 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 adhesion may be improved by wetting the surface of the capsule with a solvent or the like. When it is difficult for the powder containing the gelling agent to adhere to the surface of the soft capsule or hard capsule, the adherence of the powder can be improved by, for example, wetting the surface of the capsule. As another coating method, the capsule surface can be coated by spraying a gelling agent-dissolved solution onto a soft capsule or hard capsule. The capsule may be a hard capsule, but a soft capsule is particularly preferred. 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, still more preferably 90% or more, and most preferably the entire surface is covered.

When the solid formulation of this embodiment is a pill, it is preferred that the pill has a bare pill containing a gelling agent. Such bare pills exhibit sliminess when the surface comes into contact with water. In general, a bare pill refers to a pill without a coating layer formed on its surface. Since the pill contains a gelling agent in the bare pill, particularly in the outermost surface of the pill, the surface of the plain pill becomes slimy when in contact with a liquid medium such as water. This makes the pill easy to swallow without providing a coating layer. Pills, which are bare pills, do not have a coating layer that covers the entire surface of the pills, so there is the advantage that the pills can be prevented from becoming large and the manufacturing cost can be reduced.

When the solid preparation of this embodiment is 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 onto a core powder, a powder having a part of the surface covered with a coating layer containing the gelling agent can be obtained.

In order to achieve the sliminess and disintegration time described above, preferred components and compositions used in the solid preparation of the present embodiment are described in detail below.
The following components and composition of the solid preparation are the components and composition 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 core tablet, and the following ingredients and composition of the solid preparation correspond to the components and composition contained in the core tablet that constitutes the tablet.

Solid preparations are blended with gelling agents for the purpose of increasing surface lubricity by contact with aqueous liquids. As the gelling agent contained in the solid preparation, a powdery (particulate) substance that exhibits sliminess when containing a liquid medium such as water is used. Examples of gelling agents include xanthan gum, locust bean gum, guar gum, mannan, glucomannan, hyaluronic acid, agar, alginic acid, tamarind gum, psyllium seed gum, tara gum, carrageenan, acacia gum, arabic gum, gati gum, tragacanth gum, and karaya gum. , cassia gum, rhamzan gum, welan gum, macrohomopsis gum, curdlan, pullulan, gellan gum (deacylated gellan gum, native gellan rum), pectin, and natural polysaccharides such as soybean polysaccharides; protein hydrolyzates such as collagen; polyglutamic acid, etc. polyamino acids; biopolymers such as polylactic acid and polyglutamic acid; and at least one selected from salts and derivatives thereof. Among them, natural polysaccharides are particularly preferred.
Examples of the derivatives include hyaluronic acid derivatives, alginic acid derivatives, polyglutamic acid derivatives and the like. In addition, examples of the above salts include alginates, hyaluronates, polyglutamates, and the like. Hyaluronic acid derivatives include hyaluronic acid esters and acetylated hyaluronic acid. Examples of alginic acid derivatives include alginate and the like. Examples of polyglutamic acid derivatives include polyglutamic acid esters. Examples of alginates include sodium alginate, potassium alginate, ammonium alginate and calcium alginate. Hyaluronic acid salts include sodium hyaluronate and potassium hyaluronate. Examples of polyglutamates include sodium polyglutamate and potassium polyglutamate. Only one gelling agent may be used alone, or two or more gelling agents 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, arabic gum, gati gum, tragacanth gum, karaya gum, cassia gum, rhamzan gum, welan gum, macrohomopsis gum, curd. It preferably contains one or more selected from orchid, pullulan, gellan gum, polyamino acid, polylactic acid, and salts and derivatives thereof (hereinafter also referred to as a specific gelling agent) because it easily disintegrates in the body after ingestion. In particular, the inclusion of locust bean gum is preferable in terms of excellent disintegration ease after ingestion and a high level of both disintegration and sliminess.
In addition, combining two or more types of gelling agents is also preferable from the viewpoint of achieving compatibility between disintegration and sliminess and manufacturability, and a specific gelling agent and a gelling agent other than a specific gelling agent are combined. is more preferred. 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 agents. For example, by combining locust bean gum with xanthan gum or guar gum, it is possible to effectively enhance ease of swallowing due to sliminess. By combining locust bean gum with guar gum, it is possible to obtain a solid preparation that is excellent in disintegration in the body after ingestion.

It is preferable that the proportion of the gelling agent in the solid preparation is 0.01% by mass or more in order to sufficiently produce a slimy feeling when the solid preparation comes into contact with a liquid medium such as water. Moreover, it is preferable that the ratio of the gelling agent in the solid preparation is 70% by mass or less from the viewpoint of ease of dissolution of the active ingredient. From these points, the ratio of the gelling agent in the solid preparation is more preferably 0.1% by mass or more and 60% by mass or less, more preferably 1% by mass or more and 50% by mass or less, and 3% by mass. More preferably, it is 30% by mass or less, 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 agents in the solid preparation, the preferred range of the total mass of the specific gelling agent in the solid preparation is the gel The same ranges as the preferred ranges for the agent are included. Here, the total mass of at least one selected from the specific gelling agents is the mass of the one selected from the specific gelling agents when the solid preparation contains only one type of gelling agent. If the formulation contains two or more of these, it is the total weight of them.

When the solid preparation of the present invention contains a specific gelling agent and other gelling agents, the former in the solid preparation: the ratio of the latter is 100 mass of the latter from the viewpoint of compatibility between sliminess and disintegration. The former is preferably 10 to 1,000 parts by mass, more preferably 15 to 900 parts by mass, and particularly preferably 20 to 800 parts by mass.

For example, when the solid preparation of the present invention contains xanthan gum and locust bean gum, the former in the solid preparation: the latter ratio, from the viewpoint of increasing the sliminess and the content of the active ingredient, per 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, 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.

Further, 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 is to increase the sliminess and the content of the active ingredient. The bean gum is more preferably 10 parts by mass or more and 1000 parts by mass or less, even more preferably 15 parts by mass or more and 900 parts by mass or less, and particularly preferably 20 parts by mass or more and 800 parts by mass or less.

The solid preparation further contains one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives and starch decomposition products (hereinafter also referred to as specific excipients). It is preferable to contain By combining a gelling agent with these specific excipients, a solid formulation with excellent sliminess and 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 in terms of achieving both disintegration and sliminess, among the components described in (A) to (H) , preferably includes a combination of two or more components belonging to different categories. Specific examples include combinations of disaccharides and cellulose, combinations of disaccharides and reduced maltose, and combinations of disaccharides and starch. Further, it is more preferable to include a combination of three or more components belonging to different categories among the components described in (A) to (H). Specific examples include a combination of disaccharides, starch and cellulose, a combination of disaccharides, reduced maltose and cellulose, and the like.

Examples of sugar alcohols include monosaccharide alcohols, disaccharide alcohols, and trisaccharide or higher alcohols. Monosaccharide alcohols include, for example, tetritols such as erythritol, D-threitol and L-threitol, pentitols such as D-arabinitol and xylitol, D-iditol, galactitol (dulcitol), D-glucitol (sorbitol) and the like. hexitol, cyclitol such as inositol, mannitol, boremitol, ribitol, perseitol, D-erythro-D-galacto-octitol and the like. Examples of disaccharide alcohols include reduced maltose (maltitol), lactitol, and reduced palatinose (isomalt). Examples of trisaccharide or higher alcohols include maltotriitol, isomaltotriitol, and panitol. As the sugar alcohol, in combination with the gelling agent used in the present invention, from the viewpoint of manufacturability, such as obtaining hardness of the compressed tablet, it is preferable to use at least one selected from disaccharide alcohols. Preferably, at least one selected from reduced maltose and reduced palatinose is particularly preferred.

Monosaccharides include glucose, galactose, fructose and mannose. Among these, glucose is preferable from the viewpoint of easy availability and compatibility between disintegration and sliminess.

Disaccharides include sucrose, maltose, lactose (milk sugar), 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 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 trisaccharides or more and decasaccharides or less, preferably trisaccharides or more and decasaccharides or less, more preferably trisaccharides or more and hexasaccharides or less. Specifically, raffinose, maltotriose, melezitose, gentianose, acarbose, stachyose, galacto-oligosaccharides, fructo-oligosaccharides, mannan-oligosaccharides, isomalto-oligosaccharides (isomaltotriose, panose), xylooligosaccharides, soybean oligosaccharides, nigerooligosaccharides, and milk oligosaccharides. In particular, it is preferable to use isomalto-oligosaccharides or fructo-oligosaccharides in view of easy availability and compatibility between disintegration and sliminess.

The solid preparation preferably contains any one of monosaccharides, disaccharides and oligosaccharides from the viewpoint of taste masking and promotion of saliva secretion. In particular, solid preparations preferably contain these saccharides on the surface.

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. Examples thereof include those corresponding to crystalline cellulose described in the Japanese Pharmacopoeia Manual (published by Hirokawa Shoten), 15th Edition. Crystalline cellulose can be classified into crystalline cellulose powder and crystalline cellulose composite, and both of these can be used in the solid preparation of the present invention.

Cellulose derivatives include carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and methylcellulose. Carboxymethyl cellulose having a degree of etherification of 0.2 mol/C6 to 1.0 mol/C6 is preferable in terms of availability and compatibility between sliminess and disintegration time. More preferred is 8 mol/C6. Although the effects of the present invention can be obtained even when croscarmellose sodium or low-substituted hydroxypropyl cellulose obtained by internally cross-linking sodium carboxymethylcellulose is contained, from the viewpoint of achieving both disintegration and sliminess, cellulose derivatives More preferred are cellulose derivatives other than croscarmellose sodium and low-substituted hydroxypropylcellulose.

Starch includes native starch. Sources of starch include corn, potato, kudzu, tapioca, sweet potato, rice, wheat, wheat, barley, yam, taro, and the like. When starch is blended, it is particularly preferable to combine it with a sugar alcohol in order to achieve both disintegration and sliminess.

Examples of starch derivatives include modified starch, oxidized starch, enzyme-treated starch, pregelatinized starch, starch phosphate, distarch phosphate, starch acetate, starch octenylsuccinate, glycerol distarch, carboxymethyl starch, hydroxypropyl starch, crosslinked starch, soluble Examples include starch, grafted starch, and sodium carboxymethyl starch, and pregelatinized starch is preferred from the viewpoint of both sliminess and disintegration time. When a starch derivative is blended, it is particularly preferable to combine it 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 carboxymethylstarch is contained, the starch derivative is a starch derivative other than sodium carboxymethylstarch from the viewpoint of achieving both disintegration and sliminess. is more preferable.

Examples of starch degradation products include dextrins, preferably those having a DE of 8 to 9.5.

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 plain tablet. is preferable from the viewpoint of further increasing the content of the active ingredient, and 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 plain tablet. preferable. From these points, 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, preferably 20 parts by mass or more and 2500 parts by mass, relative to 100 parts by mass of the gelling agent in the solid formulation. It is more preferably 30 parts by mass or more and 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 preferably 70 parts by mass or less. In particular, from the viewpoint of disintegration, the specific excipient preferably accounts for 40% by mass or more, more preferably 50% by mass or more, and even more preferably 60% by mass or more in the solid preparation. , 70% by mass or more. In addition, the upper limit of the amount of the specific excipient is preferably 95% by mass or less in the solid preparation in terms of containing the gelling agent, and more preferably 90% by mass or less.

Among specific excipients, the solid preparation of the present invention contains one or more selected from monosaccharides, disaccharides, oligosaccharides, starch derivatives (particularly pregelatinized starch) and starch degradation products. It is preferable because it has high sliminess, and it is more preferable to contain monosaccharides, disaccharides, oligosaccharides or starch decomposition products.

In particular, solid preparations containing monosaccharides, disaccharides, oligosaccharides, sugar alcohols, crystalline cellulose, or cellulose derivatives (especially carboxymethylcellulose) as specific excipients have the viewpoint of excellent disintegration in addition to sliminess. and more preferably monosaccharides, disaccharides, oligosaccharides, sugar alcohols or carboxymethyl cellulose.
In addition, the inclusion of sugar alcohols and disaccharides enhances the cohesiveness of raw material powders for solid preparations, and when the solid preparation is a tablet, it is easy to formulate, such as obtaining the hardness of a compressed tablet. It is also preferable in that the effect of masking the unpleasant taste of the active ingredient can be obtained.

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

In addition, the solid preparation contains, as a specific excipient, a combination of a disaccharide and one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch and starch degradation products, thereby improving disintegration and sliminess. From the point of view of improvement, a combination of a disaccharide and an oligosaccharide or a cellulose derivative is particularly preferred. When a plain tablet contains a combination of a disaccharide and another specific excipient as a specific excipient, from the viewpoint of compatibility between sliminess and disintegration, the disaccharide is 100 parts by mass , The other specific excipient is more preferably 1 part by mass or more and 1000 parts by mass or less, more preferably 5 parts by mass or more and 300 parts by mass or less, and 5 parts by mass or more and 100 parts by mass or less is particularly preferred.

In addition, the solid preparation preferably contains a combination of sugar alcohol and starch or pregelatinized starch as a specific excipient from the viewpoint of improving disintegration and sliminess. When a solid preparation contains a combination of sugar alcohol and starch or pregelatinized starch as a specific excipient, from the viewpoint of achieving both sliminess and disintegration, starch is added to 100 parts by mass of sugar alcohol. Alternatively, the pregelatinized starch is more preferably 10 parts by mass or more and 1000 parts by mass or less, more preferably 30 parts by mass or more and 700 parts by mass or less, and particularly preferably 50 parts by mass or more and 500 parts by mass or less.

In this embodiment, containing starch, starch derivatives or starch degradation products, and combining it with xanthan gum, locust bean gum and guar gum and their salts and derivatives, especially locust bean gum, provides a balance between hardness and degree of gelation. It is preferable in that it is easier to obtain a solid preparation with good and easy swallowing.
Further, as described later, the sugar alcohol is extracted from xanthan gum, locust bean gum, guar gum, and salts and derivatives thereof under the condition that the particles containing the sugar alcohol and the gelling agent whose surface is coated with the gelling agent are not contained. A combination with at least one selected is also preferable from the viewpoint that it is easier to obtain a solid preparation that is excellent in hardness, ease of drinking, slipperiness, and is easy to swallow. and a gelling agent composed of starch and at least one selected from xanthan gum, locust bean gum, guar gum, and salts and derivatives thereof, under the condition that the coating layer of the gelling agent is not contained as described later. A solid preparation containing reduced maltose is also preferred.

The solid preparation preferably contains specific excipients in the outermost surface, and when the solid preparation is a tablet having a core tablet, it preferably contains specific excipients in the center as well.

3. Other Ingredients The solid preparation preferably contains silicon dioxide or the like as a fluidity improver. Silicon dioxide includes fine silicon dioxide and light anhydrous silicic acid. When silicon dioxide is contained, the amount of silicon dioxide is preferably 0.01 parts by mass or more and 2 parts by mass or less, more preferably 0.1 parts by mass or more and 1.8 parts by mass with respect to 100 parts by mass of the solid preparation. or less, more preferably 0.5 parts by mass or more and 1.7 parts by mass or less, and most preferably 1 part by mass or more and 1.5 parts by mass or less.

The solid preparation preferably contains a lubricant from the viewpoint of improving productivity (preventing punching during tableting). Examples of lubricants include magnesium stearate and calcium stearate. When a lubricant is contained, the proportion thereof in the solid preparation of the present invention is preferably 0.1% by mass or more and 20% by mass or less, more preferably 0.5% by mass or more and 10% by mass or less. preferable.

A solid formulation may contain an active ingredient. The active ingredient here may be a drug, or may be a functional ingredient other than a drug, or a processed product derived from plants, animals, or microorganisms. Solid formulations may contain the aforementioned active ingredients, specific excipients, silicon dioxide, disintegrants, lubricants, sugars, binders, seasonings other than sugars, emulsifiers, flavors and the like. Moreover, the solid preparation of this 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 supplements, health foods, foods with nutrient function claims, foods with function claims, foods for specified health uses, and pharmaceuticals.

The solid preparation of the present embodiment contains a seasoning and / or flavoring other than sugars on the outermost surface, thereby promoting saliva secretion when the solid preparation is included in the oral cavity, and water is added to the solid preparation. It is possible to increase the supply of liquid medium such as A sweetener, an acidulant, or the like can be used as the seasoning. As sweeteners, sucrose derivatives of sucralose, peptide sweeteners such as aspartame, alitame, 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 the flavoring agent, citrus flavors such as grapefruit flavor, lemon flavor and orange flavor, as well as fruit flavors and the like can be used.

The solid preparation according to this embodiment may contain a disintegrant. Disintegrants include, for example, baking soda (sodium hydrogen carbonate), magnesium carbonate, carmellose calcium, sodium starch glycolate, etc., which can be used as food additives, crospovidone, carboxymethyl starch sodium, croscarmellose sodium, low Substituted hydroxypropyl cellulose may be mentioned. Although the effect of the present invention is exhibited even when a disintegrant is contained, from the viewpoint of excellent sliminess, the content of the disintegrant is preferably small. The content of the disintegrant is preferably 9.9 parts by weight or less, more preferably 9 parts by weight or less, even more preferably 6 parts by weight or less, even more preferably 3 parts by weight or less, particularly preferably 1 part by weight or less, and Containment is most preferred.

Among the disintegrants, one or more disintegrants selected from crospovidone, carboxymethyl starch sodium, croscarmellose sodium or low-substituted hydroxypropyl cellulose (hereinafter these are referred to as specific disintegrants) from the viewpoint of excellent sliminess agent) is preferably as small as possible. Specifically, the amount of the disintegrant is preferably 9.9 parts by weight or less, more preferably 9 parts by weight or less, 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, 1 part by weight or less is extremely preferable, and no content is most preferable. The low-substituted hydroxypropyl cellulose is produced by reacting propylene oxide and alkali cellulose at a high temperature. means containing

The solid preparation according to this embodiment may contain particles containing a sugar alcohol and a gelling agent, the surface of which is coated with a gelling agent. Although the effects of the present invention can be exhibited even when the particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent are contained, from the viewpoint of excellent disintegration properties, the surface is coated with a gelling agent. It is preferable that the content of the particles containing the sugar alcohol and the gelling agent is small. It is preferably 10 parts by weight or less, more preferably 5 parts by weight or less, even more preferably 3 parts by weight or less, still more preferably 1 part by weight or less, and most preferably not contained. Particles containing a sugar alcohol and a gelling agent, the surface of which is coated with a gelling agent, are formed by, for example, spraying the sugar alcohol-containing particles with the gelling agent. In the present invention, the solid preparation does not contain particles containing a sugar alcohol and a gelling agent whose surface is coated with a gelling agent, and the gelling agent and a specific excipient are uniformly mixed. By doing so, it becomes easier to shorten the disintegration time.

The absence of particles containing sugar alcohols and gelling agents whose surfaces are coated with gelling agents can be confirmed, for example, by examining the distribution of gelling agents in solid preparations using cross-sectional imaging such as TOF-SIMS. can do. At this time, if the gelling agent is uniformly dispersed in the solid preparation without a layer in which the gelling agent is locally concentrated is not observed, the solid preparation of the present invention has the gelling agent on the surface. It can be said that it does not contain particles containing sugar alcohol and gelling agent coated with.

Considering ease of swallowing as a 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 methods described later.

A preferred method for producing the solid preparation of the present embodiment is further described below.
The production method of the present embodiment comprises a gelling agent and at least one selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives and starch decomposition products (specific excipients ), and it is preferable to produce tablets, particularly tablets having plain tablets, by this method.
Gelling agents, sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives and starch decomposition products include those mentioned above. In addition, the ingredients other than the gelling agent and the specific excipient in the powder containing the gelling agent and the specific excipient include the above-mentioned excipients, disintegrants, binders, lubricants, emulsifiers, effective Ingredients, seasonings, fragrances and the like are included. The preferred mass ratio of the gelling agent in the raw material powder, the preferred mass ratio of the gelling agent component, the preferred mass ratio of specific excipients, the preferred mass ratio of silicon dioxide, the disintegrant, and the lubricant are: , is the same as the preferred mass ratio of these in the solid preparation described above.

Moreover, as described above, when the tablet has a core, a raw material powder containing an arbitrary core is tableted as the raw material powder.

The raw material powder containing a gelling agent and a specific excipient may be a mixture itself of a powdered gelling agent, a powdered specific excipient, and optionally other powdered ingredients. Alternatively, it may be a granulated powder obtained by granulating a mixture of a powdery gelling agent, a powdery specific excipient, and optionally other powdery ingredients.
As a granulation method, a known granulation method used for producing tablets for oral use by a granule tableting method can be used without particular limitation.

A suitable method for producing the solid preparation of the present embodiment preferably comprises a gelling agent powder, sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives and starch decomposition products. A step of mixing with one or more powders selected from and a step of tableting the obtained mixed powder without spraying an aqueous solution in which a gelling agent is dissolved. As described above, compared to solid preparations obtained by tableting particles containing a sugar alcohol and a gelling agent, the surface of which is coated with a gelling agent, there is no such coating layer and gelation is achieved. This is because solid preparations in which agents are uniformly mixed with specific excipients, particularly plain tablets, are superior in terms of disintegration and sliminess, particularly disintegration.

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 the mixed powder obtained without spraying the mixed powder with an aqueous solution containing a gelling agent. Compressed tablets obtained by compressing the mixed powder are preferable because a solid preparation having a gelling agent present on the entire surface thereof can be easily obtained. "Tablets of mixed powder containing gelling agent and specific excipient" and "obtaining mixed powder (including gelling agent and specific excipient) without spraying aqueous solution containing gelling agent" Even if the production method is included in the expression "tablet product obtained by compressing the mixed powder", the existence form of the gelling agent and specific excipients in the bare tablet is determined according to the content described in this specification. It is not realistic to specify in more detail, and there was an impossible situation that forced us to use such an expression.

The solid preparation of the present embodiment is a solid preparation to be orally ingested, and the lubricity of the surface is increased by contact with an aqueous liquid. In particular, when the solid preparation is a tablet having a core tablet as described above, since the core tablet contains a gelling agent as described above, it is no different from a tablet having a core tablet that does not contain a gelling agent during storage. Although it has a hard property, when it comes into contact with a liquid medium such as water at the time of administration, the surface gels and becomes slimy, flexible and elastic, making it easy to swallow. In addition, when the tablets come into contact with a liquid medium such as water, the shape of the core tablet portion is maintained, and the elution of the active ingredient or the like present in the core tablet portion in the oral cavity is suppressed. As described above, the solid preparation of the present embodiment has the characteristic of swelling with a liquid medium such as water to give a slimy feel to the surface of the bare tablet.

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

(1) a gelling agent;
1 or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides, cellulose, cellulose derivatives, starch, starch derivatives and starch degradation products.

(2) The tablet according to (1), wherein the bare tablet contains one or more selected from sugar alcohols, monosaccharides, disaccharides, oligosaccharides and starch degradation 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, tragacanth gum; Polysaccharides such as karaya gum, cassia gum, rhamsan gum, welan gum, macrohomopsis gum, curdlan, pullulan, gellan gum (deacylated gellan gum, native gellan gum), pectin, and soybean polysaccharides; protein hydrolysates such as gelatin and collagen; The tablet according to (1) or (2), which is at least one selected from polyamino acids such as glutamic acid; biopolymers such as polylactic acid and polyglutamic acid; and salts and derivatives thereof.

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

(5) Tablets of any one of (1) to (4), excluding those containing crospovidone, carboxymethylstarch sodium, croscarmellose sodium or low-substituted hydroxypropylcellulose.

(6) a gelling agent;
The tablet according to any one of (1) to (5), comprising a bare tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starch and starch degradation products.

(7) locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, arabic gum, gati gum, tragacanth gum, karaya gum, cassia gum, rhamsan gum, welan gum, macrohomopsis gum, curdlan, one or more selected from pullulan, gellan gum, polyamino acids, polylactic acid, and salts and derivatives thereof;
The tablet according to any one of (1) to (6), comprising a core tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starch and starch degradation products.

(8) locust bean gum, mannan, glucomannan, hyaluronic acid, agar, tamarind gum, psyllium seed gum, tara gum, cassia gum, arabic gum, gati gum, tragacanth gum, karaya gum, cassia gum, rhamsan gum, welan gum, macrohomopsis gum, curdlan, one or more selected from pullulan, gellan gum, polyamino acids, polylactic acid, and salts and derivatives thereof;
One or more selected from xanthan gum, guar gum, alginic acid and carrageenan,
The tablet according to any one of (1) to (7), comprising a core tablet containing one or more selected from monosaccharides, disaccharides, oligosaccharides, pregelatinized starch and starch degradation products.

(9) a gelling agent;
a disaccharide;
The tablet according to any one of (1) to (8), which has a core tablet containing one or more selected from oligosaccharides, sugar alcohols, cellulose derivatives, starch and starch degradation products.

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

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

1. Evaluation of sliminess [Example 1]
As raw material powders, 400 grains of various raw materials (excluding calcium stearate) were mixed in a plastic bag according to the compounding ratio shown in Table 1, passed through a sieve, and then calcium stearate was added and mixed. This mixed powder was directly compressed with a rotary tableting machine (Kikusui Seisakusho) to obtain disk-shaped plain tablets. The hardness of the resulting plain tablet was measured with a Schleuniger tablet hardness tester. Further, when the tablet diameter (diameter) and 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. Further, the weight of one obtained plain tablet was measured and found to be 270 mg. The hardness, tablet diameter, tablet thickness and weight are the average values of the measured values for each of the three tablets.

[Example 2]
A plain tablet was obtained in the same manner as in Example 1, except that the blending ratio of the raw material powders was changed according to the blending ratio in Table 1. When the same measurements as in Example 1 were performed on the obtained plain tablet, it was found to have a hardness of 7.7 kgf, a tablet diameter of 10 mm, a tablet thickness of 3.50 mm, and a weight of 270 mg.

[Evaluation of Examples 1 and 2]
With regard to the plain tablets obtained in Examples 1 and 2, measurement of myoelectric potential in the throat at the time of ingestion and a questionnaire on ingestion sensation were conducted in a single-blind crossover study.
In addition, the slope sliding time was measured to evaluate the slipperiness of the tablets.

・Method of Taking Naked Tablet Six healthy adults who were aware that they were not good at swallowing tablets were selected as subjects (male:female ratio: 2:4). As for the dosing method, first, 4 target uncoated tablets were put in the mouth, then 20 mL of water at 22°C was put in the mouth, and the uncoated tablets were taken together with the water.

- Myoelectric potential measurement Myoelectric potential measurement was performed using an electromyograph (wireless electromyographic measurement and analysis system "Lateo" manufactured by AM Science Co., Ltd.). The measurement method followed the manual attached to the electromyograph, and specifically, it was performed as follows. Electromyograph electrodes were attached to the throat, and the subjects were asked to take 20 mL of water, the same amount as when taking the bare tablet, in order to acclimatize the throat. Next, myoelectric potential in the throat was measured when 20 mL of water was taken. After that, after taking 4 bare tablets in the mouth, 20 mL of water was taken, and the myoelectric potential of the throat was measured for each test group. The amount of muscle activity was calculated from the integral value calculated based on the obtained myoelectric potential (unit: volt (V)), and the relative value was obtained when the amount of muscle activity when only water was taken was taken as 100 (%). . The value obtained by adding up the relative values of one time per person and dividing by the number of people was defined as the amount of muscle activity (%). 1 to 3, 1 Count is 1/200 second.
The measurement in each test group was performed after a rest period of about 5 minutes, and the order of taking the bare tablets was changed for each subject.

・Questionnaire Regarding slipperiness, the lowest evaluation (-3 points) was given when the tablet did not slide down the throat and was difficult to swallow. Evaluation was made on a 7-point scale, with the highest evaluation (3 points) being the case where it was slippery enough to not get caught and was easy to drink.
For stickiness, the lowest evaluation (-3 points) is given when the tongue and pharynx are sticky and difficult to swallow. Evaluation was made on a 7-point scale with the highest evaluation (3 points).

Slope sliding time 150 ml of water per minute was supplied from the upper part of the channel to an aluminum channel with a U-shaped cross section (linear in side view, channel length 90 cm, width 1.2 cm) fixed at an inclination of 30°. 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 conducted 5 times, and the average value of the 5 times was calculated as the slope sliding down time (seconds).

Throat muscle activity (%) obtained by myoelectric potential measurement is shown in Table 1, and representative electromyograms are shown in FIGS.
Table 1 shows the average score obtained from the questionnaire and the measurement results of the slope sliding time (seconds) of the six people. In Table 1, the unit for the composition of the plain tablet is parts by mass.

As is clear from Table 1 and FIGS. 2 to 4, the plain tablets of Examples 1 and 2 suppressed the increase in throat muscle activity by about 1.5 times compared to the case of taking only water. It is a bare tablet that is easy to swallow without the need for force when ingested, with little stress on swallowing. It can be seen from the questionnaire that the bare tablets are not sticky and adhere to the tongue and pharynx, making them easy to swallow, even though they feel slippery.
In addition, the slipperiness and non-stickiness of the plain tablet containing crospovidone, carboxymethyl starch sodium, croscarmellose sodium or low-substituted hydroxypropyl cellulose are lower than those of Example 1 or 2.

In addition, when comparing the sliding down time on the slope, as shown in Table 1, Examples 1 and 2 slide down in 2 seconds or less. It turns out that it is a thing.
The plain tablet containing crospovidone, carboxymethylstarch sodium, croscarmellose sodium or low-substituted hydroxypropylcellulose has lower slope sliding property than that of Example 1 or 2.

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

2. Evaluation of disintegration [Examples 3 to 6]
According to the blending ratio in Table 1 below, the hardness is 9 kgf, the tablet diameter is 9 mm, the tablet thickness is 4.81 to 5.08 mm (Example 3 is 4.81 mm, Examples 4 and 6 are 4.89 mm, Example 5 is 5 0.08 mm) and the weight was changed to 300 mg to obtain a plain tablet in the same manner as in Example 1.
The disintegration time of the resulting bare tablet was measured by the method described below. Table 2 shows the results.

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

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

As is clear from Table 2, it was found that the plain tablet containing a gelling agent and a specific disintegrant (sugar alcohol, cellulose, cellulose derivative, starch) had a short disintegration time. Moreover, even when a specific disintegrant (crospovidone) was blended, the disintegration time was only shortened by about 20% compared to when it was not blended.

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

[Example 15]
57.1 parts by mass of sorbitol and 30.0 parts by mass of maltose are put into a fluidized bed granulator (fluidized bed granulation drying/coating machine model: FD-LAB-1, Powrex Corporation) to form a crystalline cellulose suspension. After spraying, 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 on the particle surface composed of mixed powder of sorbitol and maltose A formed particle composition (particles comprising a sugar alcohol and a gelling agent whose surface was coated with the gelling agent) was obtained.
After mixing 0.5 part by mass of calcium stearate with the obtained particle composition, tableting was performed using a rotary tableting machine (Kikusui Seisakusho), and the hardness, tablet diameter, and tablet thickness were about the same as in Examples 3 to 5. and a bare tablet weighing 300 mg was obtained. The amounts of crystalline cellulose and xanthan gum in the bare tablet were shown in Table 1.

The disintegration times of the plain tablets obtained in Examples 7-21 and Comparative Example 1 were measured in the same manner as in Examples 3-6. Table 3 shows the results.

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

<Procedure for measuring maximum stress>
The bare tablet was left still 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 tablet, and this state was maintained for 15 seconds.
A silicon tube having 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 the silicon tube is fixed while sandwiching the silicon tube in the horizontal direction. One of the plain tablets (tablet diameter 9 mm) was filled under the slits in the silicone tube. Measure the maximum stress when moving the silicon tube 20 mm upwards along the slit at a speed of 0.5 mm/sec with respect to the bare tablet using a creep meter (RE2-33005C) manufactured by Yamaden Co., Ltd. did. The cross-sectional area of the silicon tube used for measurement was 50% of the cross-sectional area of the bare tablet. When the stress exceeded 20, the measurement was terminated at that point. As the silicon tube, a square clear silicone tube manufactured by Fuso Rubber Industries, Ltd. was used. As the slits, a special cylindrical extrusion jig (AT-43446) manufactured by Yamaden Co., Ltd. was used, and these were fixed at positions where the minimum distance between them was 2 mm.
Maximum stress was determined as the mean of triplicate values.

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

As can be seen from the comparison between Examples 7 to 21 and Comparative Example 1 in Table 3, the plain tablet of Comparative Example 1, which contains only specific excipients and does not contain a gelling agent, has a gelling agent and a specific The maximum stress is greatly reduced for the bare tablets of Examples 7-21 containing the excipients.
Moreover, from the results of Examples 7 to 14, it can be seen that the maximum stress is particularly low in the case of bare tablets containing monosaccharides, disaccharides, oligosaccharides or starch degradation products among specific excipients.

Furthermore, from a comparison of Examples 15 and 16, it was found that the sugar alcohol as a gelling agent was more effective than the plain tablet obtained by compressing the particles containing the sugar alcohol and the gelling agent, the surface of which was coated with the gelling agent. It can be seen that the plain tablet obtained by mixing and tableting has a shorter disintegration time and a lower maximum stress.

In addition, compared to a bare tablet obtained by compressing particles containing a sugar alcohol and a gelling agent, the surface of which is coated with a gelling agent, a bare tablet obtained by compressing a mixture of a sugar alcohol and a gelling agent is produced. The tendency of shorter disintegration time and lower maximum stress is observed not only when sorbitol is used as the sugar alcohol, but also when sugar alcohols other than sorbitol (erythritol, mannitol, etc.) are used.

In addition, from the results of Examples 17 to 21, when locust bean gum was used as a gelling agent, the disintegration time was particularly short, and the maximum stress was low. , locust bean gum is particularly excellent among gelling agents.

The following plain tablets (formulation examples 1 to 41) were produced in the same manner as in Example 1. Both bare tablets were excellent in sliminess and disintegration. In particular, uncoated tablets that combine two or more gelling agents, uncoated tablets containing one or more selected from monosaccharides, disaccharides, oligosaccharides, starch derivatives and starch degradation products, and specific excipients Among them, plain tablets containing a combination of two or more ingredients belonging to different categories, and plain tablets combining disaccharides 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. In addition, the uncoated tablets prepared in Formulation Examples 1 to 41 were coated with sucrose, and prepared so that the ratio of the surface area of the tablet covered by the coating layer was 20% or more and less than 30% (sucrose was added using water. The tablet having the uncoated tablet (the ratio was adjusted by adhering) was also excellent in sliminess and disintegration. Similarly, the uncoated tablets prepared so that the ratio of the coating layer to the surface area of the tablet was 5% or more and less than 10% were also excellent in sliminess and disintegration.

Formulation example 42
A content liquid (95% by mass of safflower oil, 5% by mass of beeswax) was prepared, and the ratio of 16.4% by mass of glycerin, 36.8% by mass of purified water, 43.3% by mass of gelatin and 3.5% by mass of caramel color Soft capsules were obtained by filling the capsule shell (weight before drying) contained in. Encapsulation was performed by casting the capsule shell liquid to form a film, filling the inside with the content liquid, 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 per soft capsule, and the locust bean gum was adhered. Through this process, a soft capsule with a gelling agent attached to a portion of the surface was obtained.

The solid preparation of the present invention is easy to swallow and does not need to be coated on the entire surface, so it is possible to avoid an increase in size due to coating, and the manufacturing cost can be reduced by not coating. It is also excellent in ease of disintegration after ingestion. Therefore, it is clear that the solid preparation of the present invention is useful because it can be used or produced as a supplement, a health food, a food with nutrient function claims, a food with function claims, a food for specified health uses, a pharmaceutical, and the like.

Claims (1)

A solid preparation for oral ingestion,
a gelling agent;
A plain tablet containing at least one selected from sugar alcohols, cellulose, cellulose derivatives, starch, starch derivatives and starch decomposition products,
Solid preparations whose surface lubricity is increased by contact with an aqueous liquid (excluding (a), (b) and (c) described below.
(a) Those containing a particle composition containing a sugar alcohol and a water-insoluble polymer.
(a) a pharmaceutical composition in the form of a chewable sucralfate-containing tablet or dragee, characterized in that it contains at least one physiologically acceptable gel-forming agent;
(c) the following components (a), (b), (c) and (d):
(a) an agent with therapeutic activity;
(b) A gelling agent comprising a heteropolysaccharide gum and a homopolysaccharide gum capable of cross-linking each other when in contact with an environmental liquid, wherein the ratio of the heteropolysaccharide gum to the homopolysaccharide gum is 1:3 to 3: the gelling agent which is 1;
(c) an inert diluent selected from the group consisting of pharmaceutically acceptable sugars, polyhydric alcohols, industrially produced direct compression diluents, and mixtures thereof; and (d) a drug. containing a scientifically acceptable hydrophobic substance,
The ratio of the inert diluent (c) and the gelling agent (b) is 1:8 to 8:1,
controlled-release solid-dosage oral pharmaceuticals used to treat disease in patients with disease).

Images