JP2010070466A - Disintegrating tablet in oral cavity - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a disintegrating tablet in an oral cavity obtained by tablet-forming a granulated material containing &beta;-type D-mannitol crystals which is transferred from &delta;-type D-mannitol crystals, and having 0.4 to 0.9 m<SP>2</SP>/g specific surface area. <P>SOLUTION: This disintegrating tablet in the oral cavity produced through the process of transferring the &delta;-type D-mannitol crystals to the &beta;-type D-mannitol crystals by spraying water or a water-soluble solvent to a &delta;-type D-mannitol crystal-containing composition, and inhibiting the growth of the &beta;-type D-mannitol crystals formed by the above transfer, by drying the compound subjected to the above process, has a quick disintegrating property and high tablet strength. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

  The present invention relates to an orally disintegrating tablet obtained by tableting a granulated product containing a specific β-type D-mannitol crystal and having a specific specific surface area, and a method for producing the same.

  Since the conventional orally disintegrating tablet has low tablet strength, it cannot be pneumatically transported in the manufacturing process and requires manual operation. Furthermore, since powdering, chipping, and cracking are likely to occur, it is necessary to arrange a large number of inspectors, and careful attention is required for the storage state of tablets and the subdivision filling in PTP packaging. In addition, the conventional orally disintegrating tablet has low tablet strength and therefore has a high friability (referred to as friability), and a lot of powdering occurs due to friction between tablets and friction between tablets and containers. Also, chipping and cracking often occur when taking out tablets from PTP packaging for hospital pharmacy dispensing or patient use. Therefore, in dispensing, it is often impossible to make a single package using a fully automatic tablet packaging machine.

In the conventional technique, the disintegration time in the oral cavity at tablet strength (value obtained by dividing the hardness of the tablet by the fracture area) at 2 N / mm ^2, which does not cause cracking or chipping during the manufacturing process or transportation, exceeds 30 seconds. However, in order to exhibit the function as an orally disintegrating tablet, it has been a problem that the oral disintegration time is 30 seconds or less.

  An object of the present invention is to provide an orally disintegrating tablet having rapid disintegration time in the oral cavity of 30 seconds or less and exhibiting high tablet strength, and a method for producing the same.

As a result of intensive studies to solve the above problems, the present inventors contain β-type D-mannitol crystals transferred from δ-type D-mannitol crystals and have a specific surface area of 0.4 to 0.9 m ^2. Orally disintegrating tablet formed by tableting a granulated product of / g, for example, when the tablet strength is a high strength tablet of ² N / mm ² , the oral disintegration time is within 30 seconds In addition, the inventors have found a method for producing such an orally disintegrating tablet, and have further researched to complete the present invention.

That is, the features of the present invention are as follows.
(1) Disintegration in the oral cavity obtained by tableting a granulated product containing β-type D-mannitol crystals transferred from δ-type D-mannitol crystals and having a specific surface area of 0.4 to 0.9 m ² / g. Tablets.
(2) The granulated product was prepared by transferring the δ-type D-mannitol crystals in the δ-type D-mannitol crystal-containing composition to β-type D-mannitol crystals by contacting with water or a water-soluble solvent. The orally disintegrating tablet according to (1), which is a product.
(3) The orally disintegrating tablet according to (2), wherein water or a water-soluble solvent dissolves the polymer binder.
(4) The orally disintegrating tablet according to (2) or (3), wherein the content of the δ-type D-mannitol crystals in the δ-type D-mannitol crystal-containing composition is 50% by mass or more.
(5) The orally disintegrating tablet according to any one of (2) to (4), further comprising a disintegrating agent in the δ-type D-mannitol crystal-containing composition.
(6) The orally disintegrating tablet according to (5), wherein the disintegrant is selected from the group consisting of crospovidone, carmellose and low-substituted hydroxypropylcellulose.
(7) The orally disintegrating tablet according to (5), wherein the disintegrant is crospovidone.
(8) The orally disintegrating tablet according to any one of (2) to (7), further containing 5 to 30% by mass of crystalline cellulose having an aspect ratio of 3 or more in the δ-type D-mannitol crystal-containing composition.
(9) Peptic ulcer agent, neuropsychiatric agent, digestive organ agent, sleep-inducing agent, hypotension agent, migraine agent, antihypertensive agent, antipsychotic agent, or postprandial hyperglycemic agent as an active ingredient The orally disintegrating tablet according to any one of (1) to (8), which is contained.
(10) A step of transferring a δ-type D-mannitol crystal in the composition to a β-type D-mannitol crystal by bringing the δ-type D-mannitol crystal-containing composition into contact with water or a water-soluble solvent (step 1). Then, after the contact, a step (process) by fluidized bed granulation to obtain a granulated product containing the β-type D-mannitol crystals and having a specific surface area of 0.4 to 0.9 m ² / g by subjecting to a drying step. 2) And the manufacturing method of an orally disintegrating tablet containing the process (process 3) of tableting this granulated material.
(11) The production method according to (10), wherein the water or the water-soluble solvent contains a polymer binder.
(12) The production method according to (10) or (11), further comprising a disintegrant in the δ-type D-mannitol crystal-containing composition.
(13) The production method according to (12), wherein the disintegrant is selected from the group consisting of crospovidone, carmellose and low-substituted hydroxypropylcellulose.
(14) The production method according to (12), wherein the disintegrant is crospovidone.
(15) The production method according to any one of (10) to (14), wherein 5 to 30% by mass of crystalline cellulose having an aspect ratio of 3 or more is contained in the δ-type D-mannitol crystal-containing composition.

  According to the present invention, there is provided an orally disintegrating tablet having excellent properties that has a high tablet strength with very little cracking or chipping during the production process or transportation, and has an oral disintegration time of 30 seconds or less. The

In the present invention, the granulated product includes β-type D-mannitol crystals transferred from the δ-type D-mannitol crystals in an orally disintegrating tablet produced by tableting the granulated product.
The content of the δ-type D-mannitol crystal in the δ-type D-mannitol crystal-containing composition is preferably large, specifically 50% by mass or more, more preferably 60% by mass or more, Preferably it is 80 mass%. Thus, the high tablet strength and quick disintegration required for orally disintegrating tablets are more effectively achieved.

  In the context of the present invention, β- and δ-type D-mannitol crystals are D according to the X-ray diffraction pattern reported by Walter-Levy, L. [Acad. Sci. Paris t. 276 Series C, 1779, (1968)]. -Defined according to the classification of crystalline polymorphs of mannitol.

  The β-type D-mannitol crystal transferred from the δ-type D-mannitol crystal by contact with water or an aqueous solvent generally exists as a fine needle-like crystal. On the other hand, commercially available β-type D-mannitol crystals are produced as plate-like crystal powder.

  Therefore, the D-mannitol crystals contained in the orally disintegrating tablet of the present invention are β-type D-mannitol crystals transferred from δ-type D-mannitol crystals, or other β-type D-mannitol crystals. In order to distinguish between them, it is only necessary to pay attention to the crystal shape of the D-mannitol crystal using a microscope. As a result, if a fine acicular crystal is crystallized on the crystal plane, it can be recognized as a β-type D-mannitol crystal transferred from a δ-type D-mannitol crystal.

The specific surface area in the granulated product is 0.4 to 0.9 m ² / g, preferably 0.5 to 0.8 m ² / g, more preferably 0.6 to 0.7 m ² / g. The specific surface area is measured as follows.
Specific surface area measuring device Flowsorb II 2300 (Shimadzu Corporation) is used. A sample is taken in a standard cell, and measurement is performed after degassing treatment at a temperature of 40 ° C. for about 1 hour while flowing a measurement N ₂ : He = 30: 70 mixed gas. The specific surface area value is measured three times repeatedly using the same sample, and the average value is obtained.

A method for preparing the granulated product will be described.
In the present invention, the δ-type D-mannitol crystal-containing composition for preparing a granulated product is at least an active ingredient such as a medicinal component, a food ingredient, a disintegrant, crystalline cellulose, etc. in addition to the δ-type D-mannitol crystal Is included.

The types of active ingredients will be described later.
Examples of the disintegrant include crospovidone, carmellose, low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, carboxymethyl starch sodium, partially pregelatinized starch, and hydroxypropyl starch. The disintegrant is preferably 1 to 30% by mass, more preferably 3 to 20% by mass in the δ-type D-mannitol crystal-containing composition from the viewpoint of solving the contradictory problems of high tablet strength and rapid disintegration. More preferably 5 to 10% by mass is contained.

  δ-type D-mannitol crystals are known, and for example, commercially available products (Partec Delta M, Merck) may be used as they are.

  According to the present invention, the δ-type D-mannitol crystal composition may further contain crystalline cellulose in addition to the δ-type D-mannitol crystals. The larger the aspect ratio of crystalline cellulose is, the better, preferably 2 or more, more preferably 2.5 or more, and further preferably 3 or more. The aspect ratio of the crystalline cellulose is the ratio of the major axis diameter to the minor axis diameter of the crystalline cellulose, and the minor axis diameter and the major axis diameter can be easily measured by observing the crystalline cellulose with a microscope. Considering high tablet strength and rapid disintegration, the content of crystalline cellulose in the δ-type D-mannitol crystal-containing composition is preferably 5 to 30% by mass, more preferably 5 to 20% by mass. Crystalline cellulose having an aspect ratio of 3 or more is known, and commercially available products may be used as they are.

The orally disintegrating tablet of the present invention is produced through the following steps.
a step of transferring the δ-type D-mannitol crystals in the containing composition to β-type D-mannitol crystals by contacting the δ-type D-mannitol crystal-containing composition with water or a water-soluble solvent (step 1), After the contact, it is subjected to a drying step to obtain a granulated product containing the β-type D-mannitol crystals and having a specific surface area of 0.4 to 0.9 m ² / g (Step 2), and A step of tableting the granules (Step 3).

  Examples of water or a water-soluble solvent in Step 1 include purified water, methanol, ethanol, acetone, and a mixed solution thereof. Water or a water-soluble solvent may be blended with a polymer binder in order to form a granulated product more easily. Depending on the formulation, the polymeric binder is present in the form of a solution dissolved or dispersed in water or a water-soluble solvent. Examples of the polymer binder include methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, pregelatinized starch, gum arabic, agar, gelatin, tragacanth, sodium alginate, polyvinylpyrrolidone, polyvinyl alcohol, starch paste, pullulan and the like. It is done.

  The compounding quantity of a polymer binder is 1-10 mass% in water or a water-soluble solvent, Preferably it is 3-8 mass%, More preferably, it is 4-6 mass%.

As the means for contacting the δ-type D-mannitol crystal-containing composition with water or a water-soluble solvent in Step 1, the δ-type D-mannitol crystal in the δ-type D-mannitol crystal-containing composition is water or a water-soluble solvent. Any means that can wet the surface of the crystal may be used, for example, spraying or dripping of water or a water-soluble solvent. For example, a δ-type D-mannitol crystal-containing composition This is done by attaching to the grain. Fluidized bed granulation is performed using a fluidized bed granulator / dryer (for example, a fluidized bed granulator / dryer (MP-01, Paulek)), a rolling granulator (for example, a centrifugal rolling granulation coating machine (GX-20, Granurex). , Freund industry)) and the like.
The spray rate of water or a water-soluble solvent in that case is 5-15 g / min normally, Preferably it is 8-10 g / min. The amount of the liquid is preferably 5 to 55 parts by mass, more preferably 10 to 50 parts by mass, and further preferably 20 to 40 parts by mass with respect to 100 parts by mass of the δ-type D-mannitol crystals.

After the contact, it is subjected to the drying step of step 2. The drying step is performed, for example, with a fluidized bed granulator / dryer at an air supply temperature of 70 ° C. and an air volume of 40 m ³ / hour. Usually, it is carried out continuously in the fluidized bed granulation dryer used in step 1. The supply air temperature in the drying step is 50 to 80 ° C, preferably 60 to 70 ° C. Moreover, the air volume in that case is 20-60 m < ³ > / hour, Preferably it is 30-50 m < ³ > / hour. Moreover, a vacuum dryer (40-60 degreeC pressure reduction) may be sufficient.
Thus, a granulated product containing the β-type D-mannitol crystal and having a specific surface area of 0.4 to 0.9 m ² / g is obtained.

In the step of tableting the granulated product in step 3, tableting is performed by a method known per se. As the tableting machine, for example, a rotary tableting machine (VIRGO, Kikusui Seisakusho) is used. The tableting condition at that time is, for example, that the preload is 1/3 of the main pressure.
Tablet strength of the present invention is usually 2~4N / mm ^2, preferably 2~3N / mm ² approximately.
The hardness of the tablet is measured using a hardness meter (PTP 311E, Japan Machinery). The breaking area is calculated from the tablet thickness and the tablet diameter, and the tablet strength is calculated by dividing the hardness by the breaking area.

  A preferred example of the method for producing a granulated product of the present invention is a method of subjecting the δ-type D-mannitol crystal and crospovidone to coexistence in a treatment step and a drying step with water or a water-soluble solvent. The granulated product obtained by this method is preferably made to coexist with a disintegrant (especially crospovidone) by using β-type D-mannitol crystals formed by transfer of δ-type D-mannitol crystals. Thus, when tableting, fast disintegration and high tablet strength are achieved.

  In the orally disintegrating tablet of the present invention, in addition to the above-mentioned components, sweeteners, flavoring agents, excipients, fluidizing agents, lubricants, flavors, coloring commonly used in the manufacture of pharmaceuticals and foods It may further contain a material.

The sweetener is usually blended in the granulated product. Examples of the sweetener include starch sugar, reduced maltose starch syrup, sorbit, sugar, fructose, lactose, honey, xylitol, erythritol, sorbitol, saccharin, licorice and its extract, glycyrrhizic acid, sweet tea, aspartame, stevia, thaumatin and the like. It is done.
A corrigent is normally mix | blended in a granulated material. Examples of the corrigent include citric acid, tartaric acid, DL-malic acid, glycine, and DL-alanine.
The excipient is usually blended in the granulated product. Examples of the excipient include lactose, corn starch, sucrose, crystalline cellulose, anhydrous calcium hydrogen phosphate, calcium carbonate and the like.
The fluidizing agent may be included in the granulated product or may be blended at the time of tableting. Examples of the fluidizing agent include hydrous silicon dioxide, light anhydrous silicic acid, synthetic aluminum silicate, synthetic hydrotalcite, dry aluminum hydroxide gel, kaolin, calcium silicate, magnesium aluminate metasilicate, talc and the like. .
A lubricant is usually blended at the time of tableting. Examples of the lubricant include magnesium stearate, calcium stearate, stearic acid, talc, sodium lauryl sulfate, hydrogenated vegetable oil, microcrystalline wax, sucrose fatty acid ester, polyethylene glycol and the like.
The fragrance is usually blended at the time of tableting. Examples of the fragrances include strawberry, lemon, lemon lime, orange, l-menthol and mint oil.
Examples of the colorant include yellow iron sesquioxide, iron sesquioxide, edible tar dye, and natural dye.

The volume of the orally disintegrating tablet of the present invention is preferably 60 mm ³ or more, more preferably 80~500mm ^3. With such a relatively large volume orally disintegrating tablet, the effect of rapid disintegration in the oral cavity becomes more prominent.

  The orally disintegrating tablet of the present invention may be used as an orally disintegrating agent for any use as long as high tablet strength and rapid disintegration are required. For example, pharmaceuticals, foods (confectionery, functional foods, health foods) Etc.).

  When the orally disintegrating tablet of the present invention is a pharmaceutical product, the aforementioned granulated product further contains a compound having a pharmaceutical activity by oral administration, that is, an active ingredient.

  In the orally disintegrating tablet of the present invention, the active ingredient can be used without particular limitation, and examples thereof include the following.

  Hypotensive agents such as metridine: migraine therapeutic agents such as zolmitriptan: antihypertensive agents such as indapamide: antipsychotic agents: postprandial hyperglycemia improving agents: hypnotic sedation such as estazolam, triazolam, zolpidem tartrate, ramelteon Drugs, anti-anxiety drugs: antiepileptic drugs such as sodium pabronate and clobazam: antipyretic analgesics such as meloxicam, lornoxicam and loxoprofen sodium: stimulants such as methamphetamine, stimulants: anti-parxone drugs such as talipexol hydrochloride: fumaric acid Psycho-neurologic agents such as quetiabin, perospirone hydrochloride, milnacipran hydrochloride, olanzapine, paroxetine hydrochloride hydrate, etizolam: other central nervous system drugs such as edalapon, donepezil hydrochloride, tartilerin hydrate: distigmine bromide, etc. Autonomous god Agents: Antispasmodic agents such as baclofen and tizanidine hydrochloride: Ophthalmic agents such as Helenien, otolaryngological agents: Antipruritic agents such as betahistine mesylate: Cardiotonic agents such as digoxin: For arrhythmias such as allotinol hydrochloride, bisoprolol fumarate, and pilzicanide hydrochloride Agents: Diuretics such as frusemide and fluitran: Imidapril hydrochloride, cilnidipine hydrochloride, temocapril hydrochloride, losartan potassium, azelnidipine, valsartan, candesartan cilexetil, telmisartan, carvedilol, benidipine hydrochloride, enalapril succinate Vasoconstrictors such as Zolmi tribulan, Rizatriptan benzoate: Vasodilators such as amlodipine besylate, isosorbide nitrate: fluvastatin sodium, fenofibrate, Ator Statins calcium hydrate, simvastatin, pravastatin sodium and other hyperlipidemic agents: other cardiovascular agents such as ifenprodil tartrate: cough agents such as ambroxol hydrochloride, fudstein, expectorants: salmeterol xinafoate, etc. Bronchodilators: Antistagnation agents such as loperamide hydrochloride, intestinal agents: peptic ulcers such as lafutidine, omeprazole sodium, rabeprazole sodium, ecabet sodium, famotidine, lansoprazole, teprenone, repamide, etc. Bile, laxative, enemas: itopride hydrochloride, azasetron hydrochloride, ramosetron hydrochloride, ondansetron hydrochloride and other digestive organs: hormones: diabetics such as pioglitazone hydrochloride, voglibose: risedronate sodium hydrate, Metabolic drugs not classified elsewhere such as sivelestat sodium hydrate: allologic drugs such as olopatadine hydrochloride, zafirlukast, loratadine, montelukast sodium, ebastine, cetirizine hydrochloride: antibiotics such as cefcapene pivoxil, cefditoren pivoxil: Synthetic antibacterial agents such as ciprofloxacin, gatifloxacin and levofloxacin: antiviral agents such as oseltamivir phosphate and ribavirin: antifungal agents such as terbinafine hydrochloride and itraconazole: antiplatelet agents such as salvogrelate hydrochloride and ticlopidine hydrochloride. Furthermore, rhinitis drugs, motion sickness drugs, antipyretic analgesics, gastrointestinal drugs and the like contained in over-the-counter drugs can also be used as active ingredients.

  According to the present invention, a tablet exhibiting fast disintegration and high tablet strength, that is, an orally disintegrating tablet can be obtained. An orally disintegrating tablet is a tablet having an orally disintegrating property, and is a tablet having a practically sufficient disintegrating or dissolving property by saliva without taking water in the oral cavity. Specifically, for the tablet of the present invention, the time until the tablet completely disintegrates with the saliva in the mouth of a healthy adult male is usually about 10 to 30 seconds, preferably about 20 to 30 seconds.

Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.
The oral disintegration time was measured by 4 adult males. In the oral cavity, the time until the tablet completely disintegrated was measured without chewing the tablet.
The strength of the orally disintegrating tablet was determined by measuring the tablet hardness with a digital hardness meter (PTB311E, Pharm Test GmbH) and dividing the tablet hardness by the tablet breakage area.

Example 1
A mixture of 500 g of δ-type D-mannitol crystals (trade name: Partech Delta M) and 15 g of crospovidone (trade name: polyplastidone XL-10) sieved with a 42 mesh sieve was fluidized bed granulator dryer (MP- 01, Paulek). The air volume was set to 40 m ³ / hour, the supply air temperature was changed, and 135 g of purified water was sprayed from the upper part of the fluidized bed granulator / dryer at a spray rate of 10 g / min (step 1). Drying was performed at an air volume of 40 m ³ / hour (step 2), and granules 1 to 5 having different specific surface areas were produced. Each granulated product is sized with a 22 mesh sieve, 1.0% by mass of magnesium stearate (sieved with a 42 mesh sieve) is added, and mixed for 10 minutes with a V-type mixer (VL-10, Deoksugaku Kosakusho). Went. Each mixture was tableted using a rotary tableting machine (VIRGO, Kikusui Seisakusho) with a weight of φ8 mm and 170 mg so that the tablet strength was about 2.0 N / mm ² (Step 3). The tablet strength and oral disintegration time of the tablets obtained from each granulated product were examined. The results are shown in Table 1.

From the above results, it was found that when the specific surface area of the granulated product was 1.0 m ² / g or more, the oral disintegration time was 30 seconds or more.

Therefore, it was found that the specific surface area of the granulated product needs to be 0.9 m ² / g or less in order to make the oral disintegration time within 30 seconds.

(Example 2)
Table 2 shows the tablet formulation. The internally added raw material is sieved with a 42 mesh sieve and put into a fluidized bed granulator / dryer (MP-01, Paulek), and a 4% aqueous solution of PVP (polyvinylpyrrolidone, type K-29 / 32) is sprayed at a rate of 10 g / And spraying was performed under the condition of a spray amount of 125 g (step 1). Drying was performed at an air supply temperature of 70 ° C. and an air volume of 40 m ³ / hour (step 2), and sieved with a 22 mesh sieve to obtain a sized product. Light anhydrous silicic acid and magnesium stearate (both sieved with 42 mesh) and the obtained sized product were mixed for 10 minutes with a V-type mixer (VL-10, Tokuju Factory). Using a rotary tableting machine (VIRGO, Kikusui Seisakusho), the mixture was tableted with a mass of φ8 mm and a mass of 200 mg (Step 3).

The specific surface area of the granulated product was 0.5 m ² / g. The tablet strength of the obtained tablets was 2.1 N / mm ² and the oral disintegration time was 22 seconds.

(Example 3)
Table 3 shows the tablet formulation. The internally added raw material is sieved with a 42 mesh sieve, put into a fluidized bed granulator / dryer (MP-01, Paulek), and a 4% aqueous solution of PVA (polyvinyl alcohol, type EG-05) is sprayed at a rate of 10 g / min. It sprayed on the conditions of the spray amount of 125 g (process 1). Drying was performed at an air supply temperature of 70 ° C. and an air volume of 40 m ³ / hour (step 2), and sieved with a 22 mesh sieve to obtain a sized product. Light anhydrous silicic acid and magnesium stearate (both sieved with 42 mesh) and the obtained sized product were mixed for 10 minutes with a V-type mixer (VL-10, Tokuju Factory). Using a rotary tableting machine (VIRGO, Kikusui Seisakusho), the mixture was tableted with a mass of φ8 mm and a mass of 200 mg (Step 3).

The specific surface area of the granulated product was 0.6 m ² / g. The tablet strength of the obtained tablets was 2.2 N / mm ² and the oral disintegration time was 24 seconds.

Example 4
Table 4 shows the tablet formulation. The internally added raw material is sieved with a 42 mesh sieve, put into a fluidized bed granulator / dryer (MP-01, Paulek), and a 4% aqueous solution of HPC-L (hydroxypropylcellulose, type L) is sprayed at a rate of 10 g / min. Spraying was performed under the condition of a spray amount of 125 g (step 1). Drying was performed at an air supply temperature of 70 ° C. and an air volume of 40 m ³ / hour (step 2), and sieved with a 22 mesh sieve to obtain a sized product. The obtained sized product and magnesium stearate (sieved with 42 mesh) were mixed with a V-type mixer (VL-10, Deoksugaku Kosakusho) for 10 minutes. Using a rotary tableting machine (VIRGO, Kikusui Seisakusho), the mixture was tableted with a mass of φ8 mm and a mass of 200 mg (Step 3).

The specific surface area of the granulated product was 0.5 m ² / g. The tablet strength of the obtained tablets was 2.1 N / mm ² and the oral disintegration time was 23 seconds.

(Example 5)
Table 5 shows the tablet formulation. The internally added raw material is sieved with a 42 mesh sieve, put into a fluidized bed granulator / dryer (MP-01, Paulek), and a 4% aqueous solution of HPC-L (hydroxypropylcellulose, type L) is sprayed at a rate of 10 g / min. Spraying was performed under the condition of a spray amount of 125 g (step 1). Drying was performed at an air supply temperature of 70 ° C. and an air volume of 40 m ³ / hour (step 2), and sieved with a 22 mesh sieve to obtain a sized product. Light anhydrous silicic acid and magnesium stearate (both sieved with 42 mesh) and the obtained sized product were mixed for 10 minutes with a V-type mixer (VL-10, Tokuju Factory). Using a rotary tableting machine (VIRGO, Kikusui Seisakusho), the mixture was tableted with a mass of φ8 mm and a mass of 200 mg (Step 3).

The specific surface area of the granulated product was 0.7 m ² / g. The tablet strength of the obtained tablets was 2.4 N / mm ² and the oral disintegration time was 26 seconds.

(Example 6)
Table 6 shows the tablet formulation. The internally added raw material is sieved with a 42 mesh sieve, put into a fluidized bed granulator / dryer (MP-01, Paulek), and a 4% aqueous solution of HPC-L (hydroxypropylcellulose, type L) is sprayed at a rate of 10 g / min. Spraying was performed under the condition of a spray amount of 125 g (step 1). Drying was performed at an air supply temperature of 70 ° C. and an air volume of 40 m ³ / hour (step 2), and sieved with a 22 mesh sieve to obtain a sized product. Light anhydrous silicic acid and magnesium stearate (both sieved with 42 mesh) and the obtained sized product were mixed for 10 minutes with a V-type mixer (VL-10, Tokuju Factory). Using a rotary tableting machine (VIRGO, Kikusui Seisakusho), the mixture was tableted with a mass of φ8 mm and a mass of 200 mg (Step 3).

The specific surface area of the granulation product was 0.6 m ² / g. The tablet strength of the obtained tablets was 2.3 N / mm ² and the oral disintegration time was 23 seconds.

(Example 7)
Table 7 shows the tablet formulation. The internally added raw material is sieved with a 42 mesh sieve, put into a fluidized bed granulator / dryer (MP-01, Paulek), and a 4% aqueous solution of HPC-L (hydroxypropylcellulose, type L) is sprayed at a rate of 10 g / min. Spraying was performed under the condition of a spray amount of 125 g (step 1). Drying was performed at an air supply temperature of 70 ° C. and an air volume of 40 m ³ / hour (step 2), and sieved with a 22 mesh sieve to obtain a sized product. The obtained sized product and magnesium stearate (sieved with 42 mesh) were mixed with a V-type mixer (VL-10, Deoksugaku Kosakusho) for 10 minutes. The mixture was tableted using a rotary tableting machine (VIRGO, Kikusui Seisakusho) with a φ8 mm mass of 170 mg (Step 3).

The specific surface area of the granulated product was 0.6 m ² / g. The tablet strength obtained was 2.6 N / mm ² and the oral disintegration time was 14 seconds.

The present invention provides an orally disintegrating tablet having high tablet strength and rapid disintegration. According to the present invention, an orally disintegrating tablet can be produced by a conventional production method or a production method according thereto. Since no complicated or complicated method is required, the manufacturing cost can be kept low.

Claims (15)

An orally disintegrating tablet comprising a granulated product containing β-type D-mannitol crystals transferred from δ-type D-mannitol crystals and having a specific surface area of 0.4 to 0.9 m ² / g.   The granulated product is prepared by transferring the δ-type D-mannitol crystal in the δ-type D-mannitol crystal-containing composition to water or a water-soluble solvent to transfer it to β-type D-mannitol crystal. The orally disintegrating tablet according to claim 1.   The orally disintegrating tablet according to claim 2, wherein water or a water-soluble solvent dissolves the polymer binder.   The orally disintegrating tablet according to claim 2 or 3, wherein the content of the δ-type D-mannitol crystals in the δ-type D-mannitol crystal-containing composition is 50% by mass or more.   The orally disintegrating tablet according to any one of claims 2 to 4, further comprising a disintegrating agent in the δ-type D-mannitol crystal-containing composition.   The orally disintegrating tablet according to claim 5, wherein the disintegrant is selected from the group consisting of crospovidone, carmellose and low-substituted hydroxypropylcellulose.   The orally disintegrating tablet according to claim 5, wherein the disintegrant is crospovidone.   The orally disintegrating tablet according to any one of claims 2 to 7, further comprising 5 to 30% by mass of crystalline cellulose having an aspect ratio of 3 or more in the δ-type D-mannitol crystal-containing composition.   It contains a peptic ulcer agent, a neuropsychiatric agent, a digestive organ agent, a sleep induction agent, a hypotension agent, a migraine agent, an antihypertensive agent, an antipsychotic agent, or a postprandial hyperglycemia improving agent as an active ingredient. The orally disintegrating tablet according to any one of claims 1 to 8. The step of transferring the δ-type D-mannitol crystals in the composition to β-type D-mannitol crystals by contacting the δ-type D-mannitol crystal-containing composition with water or a water-soluble solvent (step 1), the contact Thereafter, a step (step 2) by fluidized bed granulation for obtaining a granulated product containing the β-type D-mannitol crystals and having a specific surface area of 0.4 to 0.9 m ² / g by subjecting to a drying step. And a method for producing an orally disintegrating tablet, comprising a step of tableting the granulated product (step 3).   The production method according to claim 10, wherein the water or the water-soluble solvent contains a polymer binder.   The production method according to claim 10 or 11, further comprising a disintegrating agent in the δ-type D-mannitol crystal-containing composition.   The production method according to claim 12, wherein the disintegrant is selected from the group consisting of crospovidone, carmellose and low-substituted hydroxypropylcellulose.   The manufacturing method of Claim 12 whose disintegrating agent is crospovidone. The manufacturing method according to any one of claims 10 to 14, wherein the δ-type D-mannitol crystal-containing composition contains 5 to 30% by mass of crystalline cellulose having an aspect ratio of 3 or more.