KR20070112043A - Orally disintegrating tablets for treating dysuria - Google Patents

Abstract

An orally disintegrating tablet is provided which gives no feeling of solid residual in mouth and has no bitter taste when being administered into mouth and be used for treating dysuria. An orally disintegrating tablet has the hardness of more than 30N, the disintegration time of less than 50 seconds and an average particle diameter of 0.5-40mum and comprises an active ingredient for treating dysuria or related diseases and 15-60 wt.% of a disintegrating agent having an average particle diameter of 105-220 mum, which includes a water-insoluble cellulose essentially composed of purified cellulose or organically modified cellulose and a super-disintegrating agent. A method for preparing the tablet comprises the steps of: (a) preparing a granule including an active ingredient; (b) preparing a mixture including the granule and a disintegrating agent; and (c) compressing the mixture into a tablet.

Description

ORALY DISINTEGRATING TABLETS FOR TREATING DYSURIA}

The present invention provides a hardness of 30N or more, comprising an active ingredient for treating urination disorders and / or related diseases having an average particle diameter in the range of 0.5 to 40 μm and a disintegrant in an amount of 15 to 60% (w / w) in the tablet. And orally disintegrating tablets having a disintegration time of 50 seconds or less and a method for producing the tablets.

Oral disintegrating or dissolving delivery systems are known in the art. One such commercially available delivery system is based on the proprietary Zydis technology (Scherer). Such systems are based on starch matrix networks or tablet-shaped lyophilized solid gelatin containing water-soluble sugars such as mannitol.

Although in tablet form, this form is actually a wafer, which is not prepared by tabletting, but is prepared by lyophilizing a solution of the components in a tablet-type “pocket”. These techniques are complex, expensive and require special equipment. Similar techniques based on lyophilization are Lyoc technique (L. Lafon) or QuickSolv technique (Janssen).

Oral disintegrating tablets prepared by tableting are also known. In general, fast disintegration is achieved by facilitating the rapid penetration of water into the tablet matrix. Basic approaches to the preparation of such tablets include maximizing the porous structure of the tablet matrix, incorporation of suitable disintegrant materials, and the use of highly water soluble excipients such as sugars or sugar alcohols. Many commercial oral tablets use excipients that have been specially treated.

Patent publication JP10298062 A, published in 1998, discloses fast disintegrating tablets comprising 13% (w / w) water insoluble excipients including doxazosin mesylate and auxiliary disintegrants and binding disintegrants. The tablet disintegrates in 50 seconds in the oral cavity and has a tablet hardness of 8.2 kgf.

Patent publication JP2004175796 A published in 2004 discloses oral preparations for treating urination disorders. The document discloses that tablets disintegrate at high speed in the mouth without a feeling of solid residue in the mouth and without an unpleasant taste upon administration, and moreover have sufficient hardness to allow the tablet to be packaged in a PTP container. The document discloses tablets comprising naphthopidyl and water insoluble excipients. When included in an amount of at least 10% (w / w), the excipient has an average particle diameter of 100 μm or less. The publication indicates that limitation of the particle diameter of the water insoluble excipient is necessary to prevent the feeling of solid residue and unpleasant taste in the mouth upon administration.

It is an object of the present invention to provide an alternative oral disintegrating tablet for the treatment of urination disorders comprising a disintegrant, without the feeling of solid residue and unpleasant taste in the mouth upon administration. This object is achieved by incorporating a disintegrant in an amount of 15 to 60% (w / w) in the tablet, wherein the average particle diameter of the disintegrant is in the range of 105 to 220 μm.

According to the present invention, an oral disintegrating type comprising an active ingredient for treating urination disorders and / or related diseases having a disintegrant in an amount of 15 to 60% (w / w) and an average particle diameter in the range of 0.5-40 μm in a tablet. As tablets, orally disintegrating tablets are prepared for the first use, wherein the disintegrant has an average particle diameter in the range of 105 to 220 μm. Surprisingly, such tablets comprising a disintegrant in an amount of 15 to 60% (w / w) having an average particle diameter in the range of 105 to 220 μm, give a feeling of solid residue in the mouth when administered as opposed to the teaching of JP2004175796 A. Do not give.

"Oral disintegration" means tablet disintegration or dispersion within 50 seconds, without disc, as measured by the in vitro disintegration test described in US Pharmacopoeia 701. These disintegration test results correlate significantly with the actual disintegration time experienced by mammals when placed in the oral cavity.

Oral disintegrating formulations for drug delivery are known in the art. The purpose of such a system is to enable the administration of solid formulations, eg tablets, of useful drugs to a patient without the need to swallow the formulation. Oral disintegrating tablets should disintegrate and selectively dissolve immediately in the oral cavity with the aid of saliva or, in some cases, a small amount of water. The resulting liquid or dispersion is then easily swallowed. This allows the dissolved or dispersed useful drug to enter the digestive tract easily and quickly. Oral disintegrating tablets should disintegrate within a time of no more than 1 minute in the oral cavity.

The tablets of the present invention disintegrate quickly when placed in the oral cavity so that there is no feeling of solid residue and unpleasant taste in the mouth. After disintegration of the preparation in the mouth, the active ingredient does not completely dissolve before swallowing with saliva.

The disintegration time of the tablets of the present invention was measured by performing a disintegration test as described in US Pharmacopoeia 701, where water was used as the test liquid. Disintegration preferably took 50 seconds or less, more preferably 30 seconds or less, particularly preferably 20 seconds or less.

The hardness of the tablets was determined by Pharmatest PTB 301 or equivalent method. The hardness of the tablets was high enough that the usual packaging and handling methods could be used. The tablet preferably has a hardness of at least 30N, more preferably at least 70N.

Active ingredients with α-1 adrenergic receptor inhibitory activity, cholinergic substances and active ingredients with muscarinic receptor antagonistic activity are typically known as active ingredients for treating urination disorders and / or diseases associated therewith. Preferred active ingredients of the present invention are naphthopidil, tamsulosin, bunazosin, urapidil, oxycilite, doxazosin, alfuzosin, woophydocin, prazosin, metazosin, piduzosin, indrazosin and pharmaceuticals of the active ingredient Acceptable salts, esters, hydrates or solvates.

YM-905 (Solifenacin Succinate; (+)-(1S, 3'R) -quinuclindin-3'-yl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2- Carboxylate Monosuccinate; International Publication No. WO 96/20194) and KMD-3213 (cylodocin; (-)-(R) -1- (3-hydroxypropyl) -5- [2- [2- [ Preference is also given to 2- (2,2,2-trifluoroethoxy) phenoxy] ethylamino] propyl] indolin-7-carboxamide: described in US Pat. No. 5387603.

Naphthopidyl, prazosin hydrochloride and urapidyl are more preferred in the present invention. Most preferred is naphthopydyl [4- (2-methoxyphenyl) piperazinyl] -3- (1-naphthyloxy) propan-2-ol].

Common naphthopidil tablets are already on the market in Japan. In a once-daily regimen, for an adult with urination disorder with prostatic hyperplasia, the initial daily dose of naphthopidil is 25 mg naphthopidil. If the patient shows an inadequate response, the dose is increased sequentially to 50-75 mg once a day or two weeks apart.

In adults with urinary obstruction with an enlarged prostate, the initial daily dose of prazosin hydrochloride is 1-1.5 mg (0.5 mg once, 2-3 times daily). If the patient exhibits an inadequate response, in a 2-3 dose regimen daily, the dose is sequentially increased to 1.5-6 mg at intervals of 1 to 2 weeks.

In adults with urination disorder with prostatic hyperplasia, the initial daily dose of urapidil is 30 mg. If the patient shows an inadequate response, in a two-dose regimen, the dose is sequentially increased to 60-90 mg at intervals of one to two weeks.

The average particle diameter of the active ingredient is determined by dispersing the active ingredient in water together with the surfactant and using a laser diffraction instrument. The active ingredient preferably has an average particle diameter in the range from 0.5 to 40 μm, more preferably in the range from 1 to 35 μm and most preferably in the range from 2 to 30 μm.

The active ingredient in the tablets of the present invention is generally up to about 50% by weight of the tablet, preferably from about 0.5 to about 35% by weight.

Tablets according to the invention further comprise a disintegrant to reduce the disintegration time. The disintegrant can be one or a combination of two or more disintegrants. Generally disintegrants comprise water insoluble cellulose, preferably the cellulose is microcrystalline cellulose. Such cellulose is preferably combined with a super-disintegrant.

The disintegrant of the present invention is present in the tablet in an amount of at least 15% (w / w), and the average particle diameter of the disintegrant is in the range of 105 to 220 μm. More preferably, the average particle diameter is in the range of 150 to 210 mu m. Most preferably the average particle diameter is in the range of 160 to 200 μm.

The tablet preferably comprises 15-60% w / w, more preferably 25-50% w / w, most preferably 35-45% w / w disintegrant.

In tablets comprising a combination of disintegrants and super-disintegrants of the water-insoluble cellulose group, the super-disintegrants are preferably at most 10% w / w, more preferably at most 8% w / w, in particular 5% It is present in an amount of w / w or less.

Disintegrants in the water-insoluble cellulose group consist essentially of purified cellulose or organically modified cellulose. Examples of such disintegrants include crystalline cellulose, microcrystalline cellulose (Avicel PH 101, Avicel PH 102, Avicel PH 301, Avicel PH 302, Avicel PH 200, Vivapur), purified wood cellulose, low-substituted hydroxypropylcellulose and Ethylcellulose. Examples of water-insoluble disintegrants not belonging to the cellulose group, which can be used are starch, partially gelatinized starch (starch 1500) and super-borin such as crosslinked polyvinylpyrrolidone, sodium starch glycolic acid, sodium carboxymethyl starch It is off.

The “average particle diameter” of the disintegrant means a diameter with a 50% sifting cumulative percentage when 75 g of powder is measured using a Retsch seiving apparatus.

Another advantage of using at least 15% (w / w) disintegrant with an average particle diameter in the range of 105 to 220 μm, preferably in the range of 150 to 210 μm, is that the disintegrant comprises an active ingredient for treating urination disorders. To improve the fluidity of the granules.

Another advantage of using at least 15% (w / w) disintegrant with an average particle diameter in the range of 105 to 220 μm, preferably in the range of 150 to 210 μm, is that tablets made more because of the higher porosity of the tablets It disintegrates at high speed.

Tablets according to the present invention are commonly used diluents (fillers) or bulking agents, including water-insoluble calcium phosphate (di- and tribasic), calcium sulfate dihydrate and calcium carbonate. ) May be included. Water-soluble diluents containing sugars and sugar alcohols are preferably used. Water soluble diluents can be used both intragranular, extragranular and intragranular. Sugars and sugar alcohols are preferably dry excipients which are ground together with the active ingredient to form a finely ground mixture prior to granulation. Examples of sugars and sugar alcohols that can be used are saccharose, glucose, fructose, lactose, mannitol, sorbitol, xylitol, erythritol, trehalose and maltitol. Lactose is the most preferred diluent for intragranular application in amounts ranging from 10 to 60% w / w in tablets.

The powdery material that is bonded together to the wet granules is a binder. The binder can be added or blended dry to the mixture to be granulated. Preference is given to binders used alone or in combination with other binders dissolved in the granulating liquid.

Examples of binders include gelatin, agar, alginic acid, sodium alginate, xanthan gum, powdered gum acacia, polyethylene glycol, hydroxypropyl cellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, partially saponified polyvinyl alcohol, Water-soluble binders such as methylcellulose, pullulan, modified starch, sugars and sugar alcohols. Preferred binders are hydroxypropyl celluloses in amounts ranging from 0.01 to 1% w / w in the tablet.

The tablet according to the invention may further comprise a substance which improves the fluidity called a fluidizing agent. For example, silicon dioxide, magnesium lauryl sulphate, magnesium aluminum silicate, magnesium oxide, talc or the like to reduce the problems associated with the flow of materials from large to small apertures in compression compressors and to reduce interparticle friction. Clay may be incorporated into the formulation.

Before compressing the tablet, most of the lubricant is added to prevent friction and wear in the process. Some lubricants also exhibit anti-sticking properties, which are appropriate properties when sticking tablet granules to the punch face and die wall. Examples of lubricant groups are magnesium stearate, calcium stearate, sucrose fatty acid esters, talc, polyethylene glycols, stearic acid, hydrogenated vegetable oils, high melting point waxes, sodium stearyl fumarate.

As sweeteners, aspartame, saccharin sodium, dipotassium glycyrizinate, stevia, taumartin can be used. These may be used alone or in combination of two or more.

The process for the preparation of oral disintegrating tablets according to the invention comprises the preparation of the granules by wet granulation of a first mixture comprising an active ingredient for treating urination disorders and / or related diseases having an average particle diameter in the range of 0.5-40 μm. A first step of producing a second mixture comprising the granules, a disintegrant in an amount of at least 15% (w / w) and a water-insoluble cellulose in a tablet, and then the second mixture is compressed into a tablet And a third step, wherein the average particle diameter of the disintegrant is in the range of 105 to 220 μm.

Methods of making the active ingredient into a particle diameter in the range within the scope of the present invention are well known in the art. For example, various grinding methods and grinders are available, including pin mill grinders, ball mill grinders, and hammer mill grinders. The production of more uniform particle diameters can be carried out, for example, by sieving.

The dry excipient and the finely ground active ingredient are mixed in a suitable mixer, preferably in a mixer in which both mixing and granulation can be carried out, for example a Gral high shear mixer.

Common mixing methods are Pharmaceutical Dosage Forms (Volume 2). Ed.H.A. Lieberman, L. Lachman, J. B. Schwartz (1990), Marcel Dekker Inc. New York and Basel pp. Disclosed in 1-71.

Granules can be prepared by dry-granulation and wet granulation. In dry-granulation, a mixture of dry excipients and the active ingredient, and optionally a lubricant (eg magnesium stearate or stearic acid) is compressed, preferably using slugging or roller compaction. A plate or disc of the mixture is obtained after compression, optionally milled into dry granules.

The preferred method of making the granules is wet granulation. A mixture comprising a granulation solution, a binder and a finely divided active ingredient is prepared and the wet mass is dried. General methods for preparing granules are described, for example, in Pharmaceutical Dosage Forms: Tablets (Volume 1). Ed.H.A. Lieberman, L. Lachman, J. B. Schwartz (1989), Marcel Dekker Inc. New York and Basel pp. Disclosed in 131-190.

Advantages of wet-granulation include improved adhesion and powder compaction, good distribution and uniform content of micronized or finely divided active ingredients, significant reduction of dust and air pollution, and prevention of separation of components.

The entire amount of disintegrant can be added to the granules just before compression, to the whole amount of powdered material before performing the wet granulation, or to the portion added before the wet granulation, and to the granules added to the dry state. You can simply divide by.

Methods of preparing tablets and other solid or dry pharmaceutical formulations are well known. For example, in the standard English textbook Gennaro et al., Remington's Pharmaceutical Sciences, (see 20th ed., Mack Publishing Company, 2000, in particular Part 5: Pharmaceutical Manufacturing), methods of making tablets, capsules and pills and their respective components. Is disclosed.

Granules and tablets produced by granulation are composed of several inert materials generally found in solid oral dosage forms. These ingredients are excipients that impart desirable physical properties to the final tablet, such as diluents, sugars and sugar alcohols, binders, glidants, sweeteners and lubricants, and excipients that help the formulation have satisfactory process and compression properties, and disintegrants and pigments. Can be classified as

The amount of moisture can vary and depends on the drying conditions applied. However, tablets generally always contain trace amounts of water up to 10% by weight, preferably about 0.5 to 10% by weight.

The invention will be further illustrated through the following non-limiting examples.

Example  One

With the compositions described in Table 1, fast disintegrating tablets were prepared on a 1 kg scale (batch A, B, C and D).

Particle diameter

Grinded mixture of naphthopidyl and lactose: Naphthopidyl was mixed with lactose (1: 1) and ground with a hammer mill. The average particle diameter of naphtopidyl in the milled mixture was 12 μm. The ground mixture was used for the preparation of batches A, B, C and D.

The average particle diameter of the applied microcrystalline cellulose (Avicel ph 200) was 195 μm.

The preparation method of batch A is as follows: The ground mixture portion of naphthopidyl and lactose is transferred to a high shear mixer and dry mixed for about 1 minute. After mixing the mixture was granulated with 2w / w% HPC solution in water for about 7 minutes. The wet granules were transferred to a liquid bed and dried for about 20 minutes at an injection temperature of 60 ° C. until the desired moisture content was reached. Dry lactose / naphthopidyl granules were then transferred to Comil and sieved to remove lumps. The filtered granules and other excipients were then transferred to Rhonrad and mixed for about 15 minutes. Finally magnesium stearate was added to the mixture in Rhonrad and mixed for about 2 minutes. Rotary compressors were used to make tablets from the granule mixture.

The preparation method of batch B is as follows: Tablets are prepared from the pulverized mixture portion of naphthopidyl and lactose, which are then broken in a high shear mixer. The resulting mixture of naphthopidyl and lactose and other excipients were transferred to Rhonrad and mixed for about 15 minutes. Finally magnesium stearate was added to the mixture in Rhonrad and mixed for about 2 minutes. Rotary compressors were used to make tablets from the granule mixture.

The process for preparing batch C is as follows: The ground mixture portion of naphthopidyl and lactose is transferred to a high shear mixer and dry mixed for about 1 minute. After mixing the mixture was granulated for about 7 minutes with 2w / w% HPC solution in water. The wet granules were transferred to a liquid bed and dried for about 20 minutes at an injection temperature of 60 ° C. until the desired moisture content was reached. The dry lactose / naphthopidyl granules were then transferred to Comil and sieved to remove lumps. The filtered granules and other excipients (including calcium silicate) were then transferred to Rhonrad and mixed for about 15 minutes. Finally magnesium stearate was added to the mixture in Rhonrad and mixed for about 2 minutes. Rotary compressors were used to make tablets from the granule mixture.

The preparation of batch D is as follows: The ground mixture portion of naphthopidyl and lactose was transferred to a high shear mixer and dry mixed with polyethylene glycol for about 1 minute. After mixing the mixture was granulated at high 600 rpm where polyethylene glycol melted to form granules. The granules were cooled to solidify the polyethylene glycol when the desired granule size distribution was obtained. The granules were then transferred to a comil and sieved to remove lumps. The filtered granules and other excipients were then transferred to Rhonrad and mixed for about 15 minutes. Finally magnesium stearate was added to the mixture in Rhonrad and mixed for about 2 minutes. Rotary compressors were used to make tablets from the granule mixture.

Batch description A dry mix mg / tab. B dry mix / slugging mg / tab. C wet granulation / ca-silicate mg / tab. D melt granulation mg / tab. Naphthopidil 75 75 75 68 Lactose 75 75 75 68 Crospovidone (Kollidon CL)  7.5  7.5  7.5  7 Talc 2.5 2.5 2 Aerosil 1.25 1.25 1.25 One Magnesium stearate 2.5 2.5 2.5 2 Microcrystalline Cellulose (Avicel ph 200)  88.75  86.25  61.25  56 Hydroxypropyl Cellulose (Shinetsu HPC-L) Polyethylene Glycol 2000 45 Calcium silicate 25

The disintegration time of all formulations was within 20 seconds with the test described in Pharmacopoeia 701. The physical properties of the resulting tablets are shown in Table 2.

Explanation Longitude (N) Weight (g) RSD A Dry mix 43 0.258 5 B Dry mixing / slugging 52 0.257 One C Wet granulation / ca-silicate 49 0.259 2 D Melt granulation 61 0.249 4

The method for producing a fast disintegrating tablet according to the present invention is a dry mixing method. Preferred manufacturing methods are melt granulation and dry mixing / slugging methods and wet granulation methods with addition of calcium silicates. The most preferred method for preparing the high speed disintegrating tablets according to the invention is the wet granulation method.

Example  2

Preparation of Rapid Disintegrating Tablets on 108 kg Scale by Wet Granulation Process

Similar to Example 1, with the compositions described in Table 3, fast disintegrating tablets according to the invention were prepared in a batch size of 108 kg. Naphthopidil was mixed with lactose and ground in a hammer mill. The milled mixture was then transferred to a high shear mixer (Gral 300) and dry mixed for about 1 minute. After mixing, the mixture was granulated for about 6 minutes with 2w / w% HPC solution in water. The wet granules were transferred to a liquid bed dryer (FLO 120) and dried at an injection temperature of 60 ° C. until the desired moisture content was reached. The dry lactose / naphthopidyl mixture was then transferred to a sieving device (Comil conical sieve) with other excipients and sieved to remove lumps. Then the ground mixture of lactose and naphthopidyl was transferred to a V blender (V-300) and mixed for about 15 minutes. Finally magnesium stearate was added to the mixture in the V blender and mixed for about 3 minutes. A rotary compressor (Libra (Kikusui) tabletting press) was used to make tablets from granules. Tablets containing 50 and 75 mg of naphthopidyl were prepared.

designation w / w% Naphthopidil (crushed) 27.8 Lactose (crushed) 27.8 Crospovidone Kollidon CL 3.0 Talc 1.0 Colloidal silicon dioxide 0.4 Magnesium stearate 1.1 Microcrystalline cellulose Avicel ph 200 37.8 Hydroxypropyl cellulose Nippon Soda Comp HPC-L 0.1 Aspartame 1.0 water a very small amount Total amount 100

The physical properties of the resulting tablets are shown in Table 4:

Weight (mg) n = 20 270.1 (267-274) % Coefficient of variation 0.67 Crushing Strength (N) n = 10 46 (41-58) Thickness (mm) n = 10 3.42-3.43 Disintegration time (seconds) n = 6 11-14 Fracture property (%) 0.14 Content uniformity n = 10 (%) 103 (99-105) STD (% Allowed Index) 1.9 (3.7)

Example  3

The feeling and taste of the solid residue in the mouth upon administration was tested with the fast disintegrating tablets prepared in the formulation of Example 2. Tablets of batches E, F and G were compressed with other tablet presses (Table 5). As a panelist, tablets were placed on the tongue of six healthy adult men. After disintegration on the tongue, the feel and bitter taste of the solid residue in the mouth upon administration was measured.

No feeling of solid residue in the mouth: No

Slight feeling of solid residue in the oral cavity: S

Significant feeling of solid residue in the mouth: Yes

No bitter taste: No

Slight bitter taste: S

Significant bitter taste: Yes

The average is calculated from the obtained results and is shown in Table 5.

arrangement E F G Tableting pressure (kN) 3.9-4.3 4.1-4.5 6.3-6.6 Tablet Hardness (N) 43 (36-50) 44 (36-52) 69 (65-74) Disintegration time (seconds) 9-11 6-8 14-16 Feeling of solid residues in the oral cavity No No No bitter No No No

According to the present invention, an oral disintegrating type comprising an active ingredient for treating urination disorders and / or related diseases having a disintegrant in an amount of 15 to 60% (w / w) and an average particle diameter in the range of 0.5-40 μm in a tablet. As tablets, orally disintegrating tablets were first made available for use with an average particle diameter of the disintegrant ranging from 105 to 220 μm. Oral disintegrating tablets of the present invention exhibit a bitter taste without giving a feeling of a solid residue in the mouth upon administration.

Claims (13)

Amounts of 15 to 60% (w / w) in active ingredients and tablets for treating urination disorders and / or related diseases having a hardness of 30 N or more and a disintegration time of 50 seconds or less and an average particle diameter in the range of 0.5-40 μm. An oral disintegrating tablet comprising a disintegrant, wherein the disintegrant has an average particle diameter in the range of 105 to 220 µm. The orally disintegrating tablet according to claim 1, wherein the disintegrant has an average particle diameter in the range of 150 to 210 μm. The orally disintegrating tablet according to claim 1, wherein the disintegrant has an average particle diameter in the range of 160 to 200 μm. The orally disintegrating tablet according to any one of claims 1 to 3, wherein the amount of the disintegrant in the tablet is 25 to 50% (w / w). The orally disintegrating tablet according to any one of claims 1 to 4, wherein the amount of the disintegrant in the tablet is 35 to 45% (w / w). The orally disintegrating tablet according to any one of claims 1 to 5, wherein the disintegrant comprises a water-insoluble cellulose and a super-disintegrant consisting essentially of purified cellulose or organic modified cellulose. . The orally disintegrating tablet according to claim 6, wherein the water insoluble cellulose is microcrystalline cellulose. 8. The orally disintegrating tablet according to claim 6 or 7, wherein said super-disintegrant is crospovidone. The orally disintegrating tablet according to any one of claims 1 to 8, wherein the tablet comprises lactose. 10. The orally disintegrating tablet according to any one of claims 1 to 9, wherein the active ingredient is naphthopidyl. The method according to any one of claims 1 to 10, obtained by preparing granules comprising the active ingredient, preparing a mixture comprising the granules and a disintegrant, and compressing the mixture into tablets. Oral disintegrating tablets that can. 12. The orally disintegrating tablet according to claim 11, wherein said granules are prepared by wet granulation of a finely ground mixture comprising the active ingredient and a water soluble diluent. In a first step, the granules are prepared by wet granulation of a first mixture comprising the active ingredient for treating urination disorders and / or related diseases having a particle diameter in the range of 0.5-40 μm, and in a second step, A second mixture comprising a disintegrant in an amount of at least 15% (w / w) in granules and tablets is prepared, and then in a third step, the second mixture is compressed into tablets. A method for producing an oral disintegrating tablet according to any one of claims 12 to 12, wherein the average particle diameter of the disintegrant is in the range of 105 to 220 µm.