KR20160145904A

KR20160145904A - Preparation method for rapidly dissolving tablet containing phloroglucinol anhydrous with improved stability

Info

Publication number: KR20160145904A
Application number: KR1020150082034A
Authority: KR
Inventors: 양재권; 조영우; 추성남; 이연주; 이지은; 임훈재; 최소라; 이현구; 오지훈
Original assignee: 대화제약 주식회사
Priority date: 2015-06-10
Filing date: 2015-06-10
Publication date: 2016-12-21
Also published as: KR101758451B1

Abstract

The present invention relates to a process for preparing tablets containing anhydrous phloroglucinol as an active ingredient, and more particularly to a process for producing tablets by mixing a phloroglucinol anhydride as an active ingredient with a disintegrant and a pharmaceutically acceptable additive, Wherein the tablets produced by the method are rapidly disintegrated by oral saliva.
In addition, according to the process for preparing tablets according to the present invention, additives which are excellent in compatibility with the active ingredient are used, and the chemical stability of the preparation is greatly improved by blocking the contact with water in the manufacturing process.

Description

[0001] The present invention relates to a method for preparing a fast-dissolving tablet containing phloroglucinol anhydrous with improved stability,

The present invention relates to a process for the production of tablets containing phloroglucinol (chemical name: 1,3,5-trihydroxybenzene) anhydride as an active ingredient, and more particularly to a process for the production of tablets containing phloroglucinol anhydride The present invention relates to a method for preparing an oral tablets having improved stability, which is prepared by a direct compression method by mixing tablets, capsules, tablets, capsules, and pharmaceutically acceptable additives.

Fluoroglucinol is a drug used as an antispasmodic drug in the form of anhydrous and hydrate, most of which are commercialized in tablet form.

Conventionally, methods for producing tablets include direct compression and granular compression.

The direct compression method is to prepare a solid oral dosage form by directly tabletting a uniform dry mixture prepared by mixing additives such as excipients, binders, disintegrants, etc. into crystals or powders of the active ingredient. There is no advantage.

On the other hand, the granule compression method is a method of preparing granules by mixing an active ingredient and a pharmaceutical additive and then tableting the granules. The granular compression method is usually used when the fluidity of the pharmaceutical composition is poor or when the binding force is weak. The granular compression method can be divided into a dry method and a wet method. The dry method is a method in which a slug and a sheet material made by a dry granulation method are pulverized and formed, and then a lubricant is mixed and compressed. In the wet method, an excipient, a disintegrant or the like is added to a medicine, It is a method of calibrating the granules by using a granulator to make the size of the granules constant. However, such a granulation method requires a complicated manufacturing process and requires much time and facilities as compared with the direct compression method. Also, there is a high likelihood that the active ingredient will be degraded during the granulation process. Thus, for this reason, the direct compression method is considered to be economical and ideal.

On the other hand, fluoroglucinol-containing tablets are dissolved by sublingual administration or taken with water.

However, when it is taken with water, the active ingredient and excipient constituting the tablet are not dissolved within a short time, and remain in the stomach, so that the drug can not be maximally used.

In addition, the active ingredient, phloroglucinol, is unstable when heat is applied in the presence of moisture, which causes a problem in storage stability of products such as discoloration of tablets due to color change.

Therefore, rapid availability of the tablet should be ensured so as to maximize the dosage of the drug, and a high quality product should be produced by a general tablet production method.

The present inventors have focused on the chemical properties of fluoroglucinol having water and heat-labile properties, and have found that by mixing a pharmaceutical additive which has a fluoroglucinol anhydride as an active ingredient and contributes to the chemical stability of the active ingredient, It is possible to produce tablets of excellent quality at the time of molding, thereby completing the present invention.

Korea Patent Office Registration No. 10-0399483 (published on September 29, 2003)

SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a method for producing a tablet capable of securing the chemical stability of a fluoroglucinol-containing tablet having water and heat-labile properties, and a tablet .

Further, the present invention is to provide an easily available tablet which is rapidly disintegrated in the oral cavity and is excellent in hardness and grindability.

In order to accomplish the above object, the present invention provides a pharmaceutical composition comprising: a first step of mixing an effective amount of a fluoroglucinol anhydride, a disintegrant, and a pharmaceutically acceptable additive; And a second step of tableting the mixture by direct compression method.

According to one embodiment of the present invention, the first step is characterized by mixing 10 to 90% by weight of anhydrous phloroglucinol, 2 to 15% by weight of a disintegrant and a pharmaceutically acceptable additive.

According to another embodiment of the present invention, the disintegrant is selected from the group consisting of low-substituted hydroxypropyl cellulose, natural starch, modified starch, pregelatinized starch, partially pregelatinized starch, pregelatinized starch, And crospovidone. &Lt; IMAGE >

According to another embodiment of the present invention, the pharmaceutically acceptable additive is selected from the group consisting of excipients, binders, lubricants, stabilizers, and surfactants.

According to another embodiment of the present invention, the excipient is selected from the group consisting of sucrose, ribose, lactose, mannitol, sorbitol, maltitol, maltol, isomalt isomalt, xylitol, erythritol, cyclodextrin, and ludipress.

According to another embodiment of the present invention, the lubricant is selected from the group consisting of talc, sodium benzonate, sodium stearyl fumarate (Pruv), calcium stearate, magnesium stearate the composition is selected from the group consisting of magnesium stearate, zinc stearate, glyceryl behenate, stearic acid and glyceryl monostearate.

According to another embodiment of the present invention, the disintegrant and the pharmaceutically acceptable additive do not contain a metal salt.

According to another embodiment of the present invention, the pressing pressure in the second step is 20 kN or less.

The present invention also provides an oral tablet characterized in that it is produced by the above method and is disintegrated by saliva within 3 minutes.

According to one embodiment of the present invention, the oral tablet has a hardness of 9.0 kp or more and a degree of grindness of 0.3% or less.

According to another embodiment of the present invention, the tablet for oral use is oral cavity disintegrating tablet or squeezing tablet.

The tablets according to the present invention contain anhydrous form of anhydrous form of phloroglucinol as an active ingredient and use an additive excellent in compatibility with an active ingredient and in that the drug is not subjected to moisture and heat in the manufacturing process, The chemical stability of the preparation is greatly improved, and the properties and stability of the tablet are excellent.

The tablets prepared by the method of the present invention can be rapidly disintegrated in the oral cavity, thus maximizing the bioavailability of the drug, producing tablets having a high hardness and high degree of abrasion, have.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a photograph showing changes in property stability of tablets according to Example 1 of the present invention. FIG.
Fig. 2 is a photograph showing a change in property stability of tablets according to Comparative Example 1. Fig.
Fig. 3 is a photograph showing a change in property stability of tablets according to Comparative Example 5. Fig.

Hereinafter, the present invention will be described in detail.

The present invention relates to a pharmaceutical composition comprising a first step of mixing an effective amount of a fluoroglucinol anhydride, a disintegrant, and a pharmaceutically acceptable additive; And

And a step of subjecting the mixture to a direct compression method to prepare an oral tablet.

The preparation method of the present invention first admixes an effective amount of a fluoroglucinol anhydride, a disintegrant, and a pharmaceutically acceptable additive.

An "effective amount" of the above-mentioned fluoroglucinol anhydrate means an amount that stops or reduces the progress of the symptom to be treated or otherwise fully or partially treats or alleviates the symptom. Such an amount can be determined by a person skilled in the art from an appropriate effective dose test.

The oral tablets of the present invention contain an effective amount of a fluoroglucinol anhydride and a disintegrant as essential components, and in addition to the above components, additives commonly known in the art to which the present invention belongs may be included.

Specifically, 10 to 90% by weight of anhydrous phloroglucinol, 2 to 15% by weight of a disintegrant, and pharmaceutically acceptable additives.

The fluoroglucinol anhydride of the present invention can be obtained by drying the hydrated form of phloroglucinol under reduced pressure at 70 to 75 ° C for 30 to 50 hours, or is commercially available.

Since the anhydrous phloroglucinol was hygroscopic, it was difficult to use it as a pharmaceutical composition. Thus, tablets were conventionally prepared by using hydrogel of phloroglucinol.

However, tablets containing phloroglucinol hydrate have a problem in that the color of tablets is changed with the lapse of time and the storage stability of the product is remarkably lowered.

In the present invention, it has been confirmed that the stability and stability of a preparation can be remarkably improved by using tablets of a direct compression method in which fluoroglucinol anhydride is used as an active ingredient and there is no contact between water and heat, and the process is simple and the present invention has been completed.

In one embodiment of the present invention, the disintegrants and pharmaceutically acceptable additives do not contain a metal salt to improve the stability of the formulation, since dark brown spots are formed when the additive comprises a metal salt.

Examples of such metal salts include alkali metal salts and alkaline earth metal salts.

Examples of the alkali metal salt include sodium benzoate, sodium alginate, sodium ascorbate, sodium aspartate, sodium hydrogen carbonate, sodium hydrogen sulfite, sodium carbonate, carboxymethylstarch sodium, sodium carboxymethylcellulose, carmellose sodium, Sodium dihydrogenphosphate, sodium dihydrogenphosphate, sodium dihydrogenphosphate, sodium dihydrogenphosphate, sodium erysorbate, sodium hydroxide, sodium lauryl sulfate, sodium DL-malate, sodium pyroisulfate, sodium oleate, sodium polyphosphate, sodium salicylate Sodium salt of sodium DL-tartrate, sodium L-tartrate and the like; and potassium salts such as carmellose potassium, potassium carbonate, potassium hydrogen tartrate, potassium carbonate, potassium chloride and potassium sorbate.

Examples of the alkaline earth metal include calcium salts such as calcium acetate, calcium carbonate, calcium chloride, carmellose calcium, calcium citrate, calcium gluconate, calcium lactate, calcium monohydrogenphosphate, calcium silicate, calcium stearate, ; Magnesium salts such as magnesium metasilicate aluminate, magnesium aluminosilicate, magnesium carbonate, magnesium chloride, magnesium hydroxide, magnesium alumina hydroxide, magnesium oxide, magnesium silicate and magnesium stearate. Natural products containing an alkali metal salt and / or an alkaline earth metal salt such as talc can be mentioned.

The additive which does not contain the metal salt of the present invention means that it contains no additive consisting of a metal salt at all or contains a small amount of the additive to the extent that the stability of the preparation is not impaired. Specifically, the content of the metal salt in the additive may be 0 to 10 parts by weight, more preferably 0 to 5 parts by weight, and particularly preferably 0 part by weight, relative to 100 parts by weight of the fluoroglucinol anhydride.

The disintegrant of the present invention plays a role in accelerating the decomposition of tablets when placed in an aqueous environment or saliva, and examples of disintegrants that can be used in the preparation method of the present invention include low- substituted hydroxypropylcellulose (low- substituted hydroxypropyl cellulose (L-HPC), natural starch, modified starch, pregelatinized starch, partially gelatinized starch, pregelatinized starch and crospovidone, preferably low-substituted hydroxypropylcellulose .

The process for preparing tablets according to the present invention may further comprise pharmaceutically acceptable additives in addition to the above components, which affect the oral disintegration or swallowing ability of tablets.

Examples of the pharmaceutically acceptable additives include excipients, binders, lubricants, stabilizers, surfactants, and the like.

The excipient is an additive which is used for the purpose of dilution or enlargement. Specific examples thereof include sucrose, ribose, lactose, mannitol, sorbitol, maltitol, maltol maltol, isomalt, xylitol, erythritol, cyclodextrin, and ludipress, and preferably Rudy presses containing lactose or lactose can be used .

The binder serves to impart a suitable hardness to the tablet for tableting, and may be selected from the group consisting of starch such as potato starch, wheat starch or corn starch, polyvinylpyrrolidone (povidone), polyvinyl alcohol and copovidone Or a combination thereof.

The lubricant is an additional excipient that can affect the disintegrating action of the tablet, for example, talc, sodium benzonate, sodium stearyl fumarate (Pruv), calcium stearate For example, calcium stearate, magnesium stearate, zinc stearate, glyceryl behenate, stearic acid and glyceryl monostearate. And magnesium stearate and talc are preferably used from the viewpoint of pharmaceutical stability.

Next, in the production method of the present invention, the mixture of step 1 is directly compressed to prepare an oral tablet.

The "direct compression method" is a concept in contrast to the "granule compression method" which is a method of directly granulating a dry mixture of an active ingredient and an additive, and then granulating the granule with an active ingredient and additives.

The direct compression method can be performed using a rotary tablet machine, and the tableting pressure can be performed at a pressure of 20 kiloNytons (kN) or less, preferably 3 to 15 kilo Newtons.

Particularly, in the manufacturing method of the present invention, the disintegration pressure and stability of the tablets can be more efficiently maintained by adjusting the tableting pressure to a proper level.

The present invention provides an oral tablet containing phloroglucinol, prepared by the above-described production method.

The manufactured oral tablets are characterized by being disintegrated by saliva within 3 minutes, and the color is not changed during circulation and storage.

In addition, the tablets of the present invention containing anhydrous phloroglucinol had a hardness of 9.0 kp or more and a degree of corruption of 0.3% or less.

Specifically, the oral tablets according to the present invention are fast-dissolving tablets for oral administration such as oral or sublingual.

Hereinafter, the present invention will be described in detail with reference to Examples.

However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited by the following examples.

< Example 1> Fluoroglucinol Using an anhydride and direct compression method Quickness Manufacture of tablets

A mixture of 289 g of lactose, 20 g of low-substituted hydroxypropylcellulose and 3 g of magnesium stearate was mixed with 124 g of phloroglucinol anhydrous, and a 10 mm round concave punch was set on a rotary tablet press and compressed at a pressure of 8 kilo Newtons to obtain an oral tablet .

< Example 2> Fluoroglucinol Using an anhydride and direct compression method Quickness Manufacture of tablets

284 g of Rudy Press, 20 g of low-substituted hydroxypropylcellulose, 2 g of magnesium stearate and 6 g of talc were mixed with 124 g of phloroglucinol anhydride, and then a 10 mm round concave punch was set on a rotary tablet press and compressed at a pressure of 8 kilo Newtons. Was prepared.

< Example 3> Fluoroglucinol Using an anhydride and direct compression method Quickness Manufacture of tablets

284 g of Rudy Press, 20 g of low-substituted hydroxypropylcellulose, 2 g of magnesium stearate and 6 g of talc were mixed with 124 g of phloroglucinol anhydride, and then a 10 mm round concave punch was set on a rotary tablet press and compressed at a pressure of 5 kilo Newtons, Was prepared.

< Example 4> Fluoroglucinol Using an anhydride and direct compression method Quickness Manufacture of tablets

284 g of Rudy press, 20 g of low-substituted hydroxypropyl cellulose, 2 g of magnesium stearate and 6 g of talc were mixed with 124 g of phloroglucinol anhydrous, and then a 10 mm circular concave punch was set on a rotary tablet press and compressed at a pressure of 15 kilo Newtons, Was prepared.

< Example 5> Fluoroglucinol Using an anhydride and direct compression method Quickness Manufacture of tablets

36 g of Rudy Press, 20 g of low-substituted hydroxypropylcellulose, 2 g of magnesium stearate and 6 g of talc were mixed with 44 g of phloroglucinol anhydride, and then a 10 mm round concave punch was set on a rotary tablet press and compressed at a pressure of 8 kilo Newtons. Was prepared.

< Example 6> Fluoroglucinol Using an anhydride and direct compression method Quickness Manufacture of tablets

Substituted hydroxypropylcellulose 20 g, crospovidone 16 g, magnesium stearate 2 g, and talc 6 g were mixed, and then a 10 mm round concave punch was set on a rotary tablet press and compressed at a pressure of 8 kilo Newtons, Was prepared.

< Comparative Example 1> Fluoroglucinol Hydrate and direct compression method Quickness Manufacture of tablets

A mixture of 253 g of lactose, 20 g of low-substituted hydroxypropylcellulose, and 3 g of magnesium stearate was mixed with 160 g of hydroglobulin of phloroglucinol (124 g as anhydrous), and then a 10 mm circular concave punch was set on a rotary tablet press, compressed at a pressure of 8 kilo Newton, Glucinol-containing oral tablets were prepared.

< Comparative Example 2> Fluoroglucinol Hydrate and direct compression method Quickness Manufacture of tablets

A mixture of 248 g of Rudy Press, 20 g of low-substituted hydroxypropylcellulose, 2 g of magnesium stearate and 6 g of talc was mixed with 160 g of hydroglycerin hydrogel (124 g as anhydrous), and a 10 mm round concave punch was set on a rotary tablet press. Followed by compression to prepare an oral tablet containing phloroglucinol.

< Comparative Example 3> Fluoroglucinol Hydrate and direct compression method Quickness Manufacture of tablets

A mixture of 248 g of Rudy Press, 20 g of low-substituted hydroxypropylcellulose, 2 g of magnesium stearate, and 6 g of talc was mixed with 160 g of hydroglobulin hydrogel (124 g as anhydrous), and a 10 mm round concave punch was set on a rotary tablet press. Followed by compression to prepare an oral tablet containing phloroglucinol.

< Comparative Example 4> Fluoroglucinol Hydrate and direct compression method Quickness Manufacture of tablets

A mixture of 248 g of Rudy press, 20 g of low-substituted hydroxypropylcellulose, 2 g of magnesium stearate and 6 g of talc was mixed with 160 g of hydroglobulin hydrogel (124 g as anhydrous), and then a 10 mm round concave punch was set on a rotary tablet press Followed by compression to prepare an oral tablet containing phloroglucinol.

< Comparative Example 5> Fluoroglucinol Anhydride and Wet granulation method Used Quickness Manufacture of tablets

289 g of lactose and 20 g of low-substituted hydroxypropylcellulose were added to a mini-mixer and mixed with 80 g of purified water to 124 g of anhydrous phloroglucinol. The resulting granules were dried in a drier and dried at 20 mesh, and 3 g of magnesium stearate was added and mixed. A 10 mm round concave punch was set on a rotary tablet machine and compressed at a pressure of 8 kilo Newton to prepare an oral tablet containing the fluoroglucinol .

The fast-dissolving tablets of Examples and Comparative Examples were compared as follows.

Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5
Active ingredient Phloroglucinol anhydride 124 124 124 124 44 392 - - - - 124 Phloroglucinol hydrate - - - - - - 160 160 160 160 - Excipient
Lactose 280 - - - - - 253 - - - 289 Rudy Press - 284 284 284 364 - - 248 248 248 - Disintegration
L-HPC 20 20 20 20 20 20 20 20 20 20 20 Crospovidone - - - - - 16 - - - - -
Lubricant Magnesium stearate 3 2 2 2 2 2 3 2 2 2 3 Talc - 6 6 6 6 6 - 6 6 6 - Binding liquid
Purified water - - - - - - - - - - 80 Anhydrous ethanol - - - - - - - - - - - Gross weight (dry weight) 436 436 436 436 436 436 436 436 436 436 436 Compression pressure 8 8 5 15 8 8 8 8 5 15 8

(Weight unit: g, pressure unit: kN)

< Experimental Example 1> Quickness Evaluation of stability of tablets

The fast-dissolving tablets prepared in the above Examples and Comparative Examples were stored for one month in accordance with the storage conditions of the Korean Pharmacopoeia Stability Test, and the stability of the tablets was tested.

Storage conditions Long-term confidentiality
(25 DEG C) Long-term / Opening
(25 캜 RH 60%) Acceleration / confidentiality
(40 DEG C) Acceleration / unsealing
(40 캜 RH 75%) Harsh and confidential
(60 DEG C) Storage period 1 month 1 month 1 month 1 month 1 week Example 1 No change No change No change Discolored No change Example 2 No change No change No change Discolored No change Example 3 No change No change No change Discolored No change Example 4 No change No change No change Discolored No change Example 5 No change No change No change Discolored No change Example 6 No change No change No change Discolored No change Comparative Example 1 No change No change Discolored Discolored Discolored Comparative Example 2 No change No change Discolored Discolored Discolored Comparative Example 3 No change No change Discolored Discolored Discolored Comparative Example 4 No change No change Discolored Discolored Discolored Comparative Example 5 No change No change Discolored Discolored Discolored

As shown in Table 2 and Figs. 1 to 3, the properties of both the tablets of Examples and Comparative Examples did not change under long-term, airtight, long-term or open condition.

However, the tablets of the present invention (Examples 1, 2, 3, 4, 5 and 6) prepared by direct compression method using the fluoroglucinol anhydride as an active ingredient were discolored only under accelerated / Tablets (Comparative Examples 1, 2, 3, and 4) prepared using a lucinol anhydride and produced by a wet granulation method (Comparative Example 5) and a direct compression method using a hydrogel of a fluoroglucinol (Comparative Examples 1, 2, 3 and 4) It was confirmed that the stability of the tablets produced by the production method of the present invention was remarkably improved because the hue changed in all cases under open, harsh and hermetic conditions.

< Experimental Example 2> Quickness Measurement of properties of tablets and Disintegration Experiment

In order to measure the physical properties of the tablets for oral use according to the present invention, the hardness and the degree of abrasion test were carried out with the readily available tablets prepared in the above Examples and Comparative Examples. The hardness was measured using SOTAX HT100, and the margins were tested using the Ki-Woo trading KW-F25 model.

The disintegration time was measured according to the disintegration test method (15 ~ 25 ℃) of the UK Pharmacopoeia.

Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Hardness 11.7kp 12.8kp 10.4kp 17.0kp 12.5kp 9.8kp 6.8kp 7.1kp 5.2kp 8.0kp 13.9kp Massono 0.09% 0.13% 0.18% 0.06% 0.13% 0.22% 1.02% 0.98% 1.12% 0.26% 0.07% Disintegration
time 1 minute 50 seconds 1 minute 40 seconds 1 minute 20 seconds 2 minutes 30 seconds 1 minute 40 seconds 1 minute 10 seconds 2 minutes 20 seconds 2 minutes 10 seconds 1 minute 10 seconds 2 minutes 40 seconds 4 minutes 50 seconds

As shown in Table 3, Examples 1 to 5 of the present invention satisfied the disintegration criterion, and were excellent in high hardness and degree of grindability. On the other hand, in the case of the comparative example, the tablets of Comparative Example 5 had a disintegration criterion And the tablets of Comparative Examples 1 to 4 were disintegrated within 3 minutes. However, the tablets were not smoothly produced due to the low hardness of 8.0 kp or less. Further, except for Comparative Example 4 using a high tabletting pressure And the yield was not good.

Claims

Mixing an effective amount of a fluoroglucinol anhydride, a disintegrant, and a pharmaceutically acceptable additive; And
Wherein the mixture is compressed by a direct compression method.

2. The method of claim 1, wherein the first step comprises mixing 10 to 90% by weight of anhydrous phloroglucinol, 2 to 15% by weight of a disintegrant, and a pharmaceutically acceptable additive.

The disintegrant of claim 1 wherein said disintegrant is selected from the group consisting of low-substituted hydroxypropyl cellulose, natural starch, modified starch, pregelatinized starch, partially pregelatinized starch, pregelatinized starch and crospovidone &Lt; / RTI > or a pharmaceutically acceptable salt thereof.

The method of claim 1, wherein the pharmaceutically acceptable excipient is selected from the group consisting of excipients, binders, lubricants, stabilizers, and surfactants.

5. The composition of claim 4, wherein the excipient is selected from the group consisting of sucrose, ribose, lactose, mannitol, sorbitol, maltitol, maltol, isomalt, A method for preparing an oral tablet, wherein the tablet is selected from the group consisting of xylitol, erythritol, cyclodextrin, and ludipress.

5. The composition of claim 4, wherein the lubricant is selected from the group consisting of talc, sodium benzonate, sodium stearyl fumarate, Pruv, calcium stearate, magnesium stearate, Wherein the tablet is selected from the group consisting of zinc stearate, glyceryl behenate, stearic acid and glyceryl monostearate.

2. The method of claim 1, wherein the disintegrant and pharmaceutically acceptable excipient do not comprise a metal salt.

The method for producing an oral tablet according to claim 1, wherein the tableting pressure in the second step is 20 kN or less.

9. An oral tablet, which is produced by the method of any one of claims 1 to 8 and is disintegrated by saliva within 3 minutes.

The oral tablet according to claim 9, wherein the tablet for oral use has a hardness of 9.0 kp or more and a degree of fatigue of 0.3% or less.

[Claim 11] The oral tablet according to claim 9, wherein the tablet for oral use is an oral cavity tablet or a tablet.