Orally disintegrating tablet comprising benzimidazole derivative compound and preparation method thereof

Abstract

To provide an orally disintegrating tablet that masks the bitterness of (S)-4-(5,7-difluorochroman-4-yloxy)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide (tegoprazan), which is used as a therapeutic agent for reflux esophagitis, and disintegrates in a short time in the oral cavity while exhibiting excellent sensory properties, and also to provide a preparation method thereof.SOLUTION: The present invention provides an orally disintegrating tablet that comprises wet granules comprising tegoprazan, a pharmaceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an orally disintegrating tablet comprising a benzimidazole derivative compound and a method for preparing the same, and more particularly to an orally disintegrating tablet containing wet granules comprising tegoprazan, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener, and a method for preparing the same. [Background technology]

[0002] Tegoprazan is (S)-4-(5,7-difluorochroman-4-yloxy)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide (or 7-{[(4S)-5,7-difluoro-3,4-dihydro-2H-chromen-4-yl]oxy}-N,N,2-trimethyl-1H-benzimidazole-5-carboxamide), a potassium-competitive acid blocker (P-CAB) with a mechanism similar to that of acid pump antagonists (APAs). It competes with potassium ions to block H, a component of gastric acid in the parietal cells of the stomach. + H, an enzyme that secretes ions into the gastric lumen + / K + -It binds to ATPase (proton pump) and thereby inhibits the secretion of gastric acid.

[0003] Tegoprazan is used as a treatment for gastroesophageal reflux disease, and more than 70% of gastroesophageal reflux disease patients are elderly people aged 60 or older who have difficulty swallowing. Many of these patients have poor swallowing ability and therefore have many difficulties taking oral dosage forms such as tablets and capsules.

[0004] Orally disintegrating tablets are convenient for such patients, but tegoprazan is a drug that has a bitter taste even at low concentrations, and there are limitations to the development of orally disintegrating tablets of tegoprazan.

[0005] Therefore, there is a need for the development of an orally disintegrating tablet that disintegrates in the oral cavity in a short period of time while masking the bitterness of tegoprazan and exhibiting excellent organoleptic properties. [Prior art documents] [Patent documents]

[0006] International Patent Publication WO2007 / 072146 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention can provide an orally disintegrating tablet containing wet granules comprising tegoprazan, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener.

[0008] The present invention can provide a method for preparing an orally disintegrating tablet, the method comprising: (1) preparing a wet granule containing tegoprazan, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener; (2) adding one or more pharma- ceutically acceptable excipients to the wet granule to prepare a mixture; and (3) compressing the mixture into a tablet.

[0009] The present invention can provide an orally disintegrating tablet prepared by the above-mentioned preparation method. [Means for solving the problem]

[0010] Terms not specifically defined herein are to be understood to have the meaning commonly used in the art to which this invention pertains. Furthermore, the singular includes the plural and vice versa, unless otherwise defined by context.

[0011] Sections are separated herein for convenience in expounding the specification, but the contents of any one section should not be construed as being dependent upon that section.

[0012] Orally disintegrating tablets The present invention can provide an orally disintegrating tablet containing wet granules comprising a compound represented by the following formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener. [ka]

[0013] The compound represented by the above formula 1 is named (S)-4-(5,7-difluorochroman-4-yloxy)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide and is called tegoprazan.

[0014] In the present invention, "a pharma- ceutically acceptable salt" may refer to a salt formed with any inorganic acid, organic acid, or base that does not cause significant irritation to a subject to which it is administered and does not impair the biological activity and physical properties of tegoprazan. The salt used herein may include salts conventionally used in the art, such as acid addition salts formed with pharma- ceutically acceptable free acids. Pharmaceutically acceptable salts include pyridinate, acetate, adipate, aspartate, benzoate, besylate, bicarbonate / carbonate, bisulfate / sulfate, borate, camsylate, citrate, cyclamate, edisylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride / chloride, hydrobromide / bromide, hydroiodide / iodide, isethionate, lactate, tetrafluoroborate ... The salt may be specifically selected from the group consisting of tetrahydrofuran, malate, maleate, malonate, mesylate, methylsulfate, naphthylate, 2-napthylate, nicotinate, nitrate, orotate, palmitate, pamoate, phosphate / hydrogenphosphate / dihydrogenphosphate, pyroglutamate, saccharate, stearate, succinate, tannate, tartrate, tosylate, trifluoroacetate, and xinafoate, but is not limited thereto. The salt may be any salt that exhibits and exerts the pharmacological activity of tegoprazan as in the past, without being particularly limited thereto.

[0015] In the present invention, the term "hydrate" refers to a compound in which tegoprazan or a pharma- ceutically acceptable salt thereof and water are bound by non-covalent intermolecular forces, and may contain a stoichiometric or non-stoichiometric amount of water.

[0016] In the present invention, the term "solvate" means a compound in which tegoprazan or a pharma- ceutically acceptable salt thereof is bound to a solvent other than water by non-covalent intermolecular forces, and may contain a stoichiometric or non-stoichiometric amount of the solvent.

[0017] As used herein, tegoprazan may refer to the compound represented by the above formula 1, as well as its pharma- ceutically acceptable salts, their hydrates or solvates, or mixtures thereof.

[0018] In the present invention, tegoprazan may exist in crystalline or amorphous form.

[0019] The orally disintegrating tablet of the present invention may contain moist granules, and the moist granules may contain the compound represented by the above formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof as an active ingredient.

[0020] The orally disintegrating tablet of the present invention can be used for the treatment of diseases mediated by acid pump antagonism due to the property of containing the compound represented by the above formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof.

[0021] The symptom may be at least one selected from the group consisting of gastrointestinal disease, gastroesophageal disease, gastroesophageal reflux disease (GERD), peptic ulcer, gastric ulcer, duodenal ulcer, NSAID-induced ulcer, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, non-erosive reflux disease (NERD), visceral referred pain, heartburn, nausea, esophagitis, dysphagia, salivation, airway lesions, and asthma, and may in particular be, but is not limited to, gastroesophageal reflux disease (GERD).

[0022] "Gastroesophageal reflux disease (GERD)" refers to a condition in which stomach contents flow back into the esophagus, causing symptoms and complications that interfere with daily life. It can be divided into erosive esophagitis (EE) and non-erosive reflux disease (NERD).

[0023] The orally disintegrating tablet of the present invention can contain a therapeutically effective amount of tegoprazan.

[0024] In the present invention, the term "therapeutically effective amount" may mean an amount effective for preventing or treating a disease mediated by acid pump antagonism.

[0025] The orally disintegrating tablet of the present invention may comprise moist granules, which may comprise a sweetener.

[0026] In the present invention, the wet granules may contain the compound represented by formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener in a weight ratio of 1:0.001 to 1:0.4.

[0027] The compound represented by formula 1, its pharma- ceutically acceptable salt, their hydrate or solvate, or a mixture thereof, and the sweetener are specifically included in a weight ratio of 1:0.001 to 1:0.4, 1:0.005 to 1:0.35, 1:0.01 to 1:0.3, and particularly 1:0.05 to 1:0.2, but are not limited thereto.

[0028] In this regard, in a specific embodiment of the present invention, when the orally disintegrating tablet of the present invention contains the compound represented by formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof and a sweetener in a weight ratio of 1:0.05 to 1:0.2, it has been confirmed that the total amount of related substances produced is reduced, thereby exhibiting excellent stability (Table 8).

[0029] In the present invention, sweeteners include sucralose, aspartame, saccharin, acesulfame potassium, stevioside, enzyme-modified stevia, sucrose, isomalt, maltitol, mannitol, sorbitol, steviol glycoside, erythritol, xylose, xylitol, lactitol, neotame, ribose, tomatine, polyglycitol, advantum, tagatose, trehalose, glucose, maltose, dextrose, sucrose, fructose, honey, glycyrrhizin, monellin, rabsoside, curculin, corn syrup, lactose, oligosaccharides, and mixtures thereof, particularly, but not limited to, sucralose, aspartame, maltitol, etc.

[0030] In this regard, in a specific embodiment of the present invention, it was confirmed that the orally disintegrating tablet of the present invention produces a small total amount of related substances, and therefore exhibits excellent stability regardless of the type of sweetener (Table 8).

[0031] In the present invention, the sweetener may be contained in an amount of 0.01 to 10% by weight, specifically 0.01 to 8% by weight, 0.07 to 6% by weight, 0.1 to 4% by weight, more specifically 0.1 to 3% by weight, and even more specifically 0.7 to 2% by weight, relative to the total weight of the tablet, but is not limited thereto.

[0032] The orally disintegrating tablet of the present invention may further contain a pharma-ceutically acceptable additive.

[0033] The term "pharmaceutical acceptable additive" refers to any additive that does not cause severe irritation to a subject to which it is administered and does not impair the biological activity and physical properties of tegoprazan. Specific examples of the additive include, but are not limited to, excipients, disintegrants, diluents, flavoring agents, sweeteners, lubricants, etc.

[0034] The orally disintegrating tablet of the present invention may further contain a disintegrant as a pharma- ceutical acceptable additive.

[0035] In the present invention, the disintegrant may be, but is not limited to, crospovidone, croscarmellose sodium, sodium starch glycolate, alginic acid, sodium alginate, low-substituted hydroxypropylcellulose, carboxymethylcellulose, corn starch, pregelatinized starch, microcrystalline cellulose, hydroxypropylcellulose, sodium bicarbonate, and mixtures thereof, particularly crospovidone.

[0036] When crospovidone is used as the disintegrant, the particle size may be specifically, but not limited to, 10 to 130 μm, more specifically, 10 to 40 μm.

[0037] In the present invention, the disintegrant may be contained in an amount of 1 to 50% by weight, specifically 1 to 40% by weight, 1 to 30% by weight, 1 to 20% by weight, 1 to 10% by weight, and more specifically 2 to 7% by weight, relative to the total weight of the tablet, but is not limited thereto.

[0038] The orally disintegrating tablet of the present invention may further comprise, as a pharma-ceutically acceptable excipient, a diluent, a flavoring agent, a sweetener, a lubricant, or a mixture thereof.

[0039] In the present invention, the diluent may be any one selected from the group consisting of mannitol, lactose, starch, microcrystalline cellulose, Ludipress (BASF), Pearlitol Flash (Roqutte), dibasic calcium phosphate, dextrose, maltose, erythritol, sucrose, maltitol, trehalose, glucose, xylitol, F-Melt (Fuji Chemical Industry Co., Ltd.), sorbitol, pregelatinized starch, anhydrous dibasic calcium phosphate, dicalcium phosphate, and mixtures thereof, and in particular may be, but is not limited to, mannitol, xylitol, Pearlitol Flash, or mixtures thereof.

[0040] In the present invention, the diluent may be present in an amount of 1 to 99% by weight, specifically 1 to 99% by weight, 5 to 97% by weight, 10 to 95% by weight, 15 to 92% by weight, and more specifically 20 to 90% by weight, based on the total weight of the tablet, but is not limited thereto.

[0041] In the present invention, the flavoring agent may be any one selected from the group consisting of peppermint flavor, yogurt flavor, fruit flavor, and mixtures thereof, specifically, but not limited to, peppermint flavor, and the fruit flavor may be specifically, but not limited to, apple flavor, grape flavor, strawberry flavor, or lemon flavor.

[0042] In the present invention, the flavoring agent may be included in an amount of 0.01 to 10% by weight, specifically 0.05 to 8% by weight, 0.1 to 6% by weight, 0.2 to 4% by weight, and more specifically 0.3 to 3% by weight, based on the total weight of the tablet, but is not limited thereto.

[0043] The orally disintegrating tablet of the present invention may further contain a sweetener in addition to the sweetener contained in the wet granules. The further sweetener may be any one selected from the group consisting of sucralose, aspartame, saccharin, acesulfame potassium, stevioside, enzymatically modified stevia, sucrose, isomalt, maltitol, mannitol, sorbitol, steviol glycoside, erythritol, xylose, xylitol, lactitol, neotame, ribose, tomatine, polyglycitol, advantum, tagatose, trehalose, glucose, maltose, dextrose, sucrose, fructose, honey, glycyrrhizin, monellin, rabsoside, curculin, corn syrup, lactose, oligosaccharides, and mixtures thereof, and in particular may be, but is not limited to, maltitol, sucralose, enzymatically modified stevia, or mixtures thereof.

[0044] The sweetener contained in the moist granules and the further sweetener contained therein may be of the same type or of different types.

[0045] In the present invention, the sweetener contained in the wet granules is referred to as the first sweetener, and the sweetener further contained therein is referred to as the second sweetener. In this case, "first", "second", etc. are used only to distinguish between multiple ingredients and do not indicate their priority.

[0046] The orally disintegrating tablet of the present invention may contain a sweetener in an amount of, but is not limited to, 0.01 to 10% by weight, specifically 0.01 to 5% by weight, and more specifically 0.1 to 3% by weight, based on the total weight of the tablet, without distinguishing between the sweetener contained in the moist granules and any further sweetener contained therein.

[0047] In the present invention, the lubricant may be any one selected from the group consisting of stearic acid, metal stearates, talc, colloidal silicon dioxide, sucrose fatty acid esters, hydrogenated vegetable oils, waxes, glycerin fatty acid esters, glycerol dibehenate, and mixtures thereof, and may be, but is not limited to, metal stearates, colloidal silicon dioxide, or mixtures thereof. More specifically, the metal stearates may be, but is not limited to, calcium stearate or magnesium stearate.

[0048] In the present invention, the lubricant may be contained in an amount of 0.1 to 10% by weight, specifically 0.1 to 10% by weight, 0.2 to 8% by weight, 0.3 to 7% by weight, 0.4 to 6% by weight, and more specifically 0.5 to 5% by weight, relative to the total weight of the tablet, but is not limited thereto.

[0049] In the present invention, the wet granules can be prepared by, but not limited to, high shear granulation or fluid bed granulation.

[0050] Wet granules include powder particles collected in a granulation liquid (binder solution), which may contain binders or additives that can provide bonding strength, either alone or in combination, to provide adhesion between the particles in the dry state.

[0051] In the present invention, the wet granules can be prepared using a binder solution containing any one selected from the group consisting of alcohol, water, and mixtures thereof, and a sweetener.

[0052] The wet granules prepared using a binder solution containing a sweetener may have tegoprazan particles and excipients intimately physically bound together within the granules, i.e., adhered / coated.

[0053] In the present invention, the binder solution may further contain a binder or an additive capable of imparting binding strength.

[0054] The binder or additive capable of imparting binding power may be any one selected from the group consisting of hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, polyethylene glycol, natural rubber, synthetic rubber, copovidone, ethylcellulose, methacrylic acid copolymers, and mixtures thereof, and in particular may be hydroxypropyl methylcellulose, but is not limited to these.

[0055] The binder or additive capable of imparting cohesive strength may be added as a solution or as a dry material mixed with the primary powder particles.

[0056] In this regard, in one specific embodiment of the invention, wet granules are prepared with a binder solution comprising 58% (w / w) ethanol and sucralose in water; a binder solution comprising 50% (w / w) ethanol and sucralose in water; a binder solution comprising 50% (w / w) ethanol, hydroxypropyl methylcellulose and sucralose in water; a binder solution comprising 50% (w / w) ethanol and maltitol in water; or a binder solution comprising 50% (w / w) ethanol and aspartame in water; etc.

[0057] The orally disintegrating tablet of the present invention can rapidly disintegrate within 30 seconds.

[0058] In this regard, in a specific embodiment of the present invention, the orally disintegrating tablet of the present invention was confirmed to disintegrate within 30 seconds in an in vitro disintegration experiment, an in vivo disintegration experiment, and a disintegration experiment using a disintegration tester (Table 2).

[0059] The orally disintegrating tablet of the present invention can exhibit excellent sensory properties with masked bitterness.

[0060] In this regard, in a specific embodiment of the present invention, the orally disintegrating tablet of the present invention has extremely little bitterness and has a sensation of softly disintegrating in the oral cavity, which has the effect of improving the bitterness and has been confirmed to exhibit excellent sensory properties (Table 3).

[0061] The orally disintegrating tablet of the present invention disintegrates in the oral cavity in a short time and exhibits excellent sensory properties such as masking the bitter taste, thereby significantly improving the patient's compliance with medication. Therefore, the orally disintegrating tablet of the present invention is considered to be effective in treating patients with gastroesophageal reflux disease, particularly those with gastroesophageal reflux disease who have difficulty swallowing.

[0062] The orally disintegrating tablet of the present invention can exhibit an excellent dissolution rate.

[0063] In this regard, in a specific embodiment of the present invention, it was confirmed that the orally disintegrating tablet of the present invention exhibits an excellent dissolution rate of tegoprazan without any release delay, at a level comparable to that of the reference drug K-CAP tablet (Table 4, Figures 1 and 2).

[0064] The orally disintegrating tablet of the present invention can exhibit excellent stability.

[0065] In this regard, in a specific embodiment of the present invention, it was confirmed that the orally disintegrating tablet of the present invention produces a small total amount of related substances under stress conditions and accelerated conditions, thereby exhibiting excellent stability (Table 6).

[0066] In this regard, in a specific embodiment of the present invention, it has been confirmed that the orally disintegrating tablet of the present invention exhibits excellent appearance stability under stress and accelerated conditions without any change in appearance due to moisture or heat on the tablet surface (FIG. 3).

[0067] Method for preparing orally disintegrating tablets The present invention relates to a method for preparing an orally disintegrating tablet, comprising the steps of: (1) preparing a wet granule comprising a compound represented by the following formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener; (2) preparing a mixture by adding one or more pharma- ceutically acceptable excipients to the wet granules; and (3) compressing the mixture into a tablet. [ka]

[0068] In the method for preparing an orally disintegrating tablet of the present invention, the contents described in the above section on orally disintegrating tablets can be similarly applied unless there is a contradiction. Therefore, the wet granules of the orally disintegrating tablet, the components contained therein, the content of each component, the weight ratio of each component, the uses, effects, etc. can be directly applied to the method for preparing an orally disintegrating tablet of the present invention unless there is a contradiction.

[0069] In the present invention, the sweetener may be any one selected from the group consisting of sucralose, aspartame, saccharin, acesulfame potassium, stevioside, enzyme-modified stevia, sucrose, isomalt, maltitol, mannitol, sorbitol, steviol glycoside, erythritol, xylose, xylitol, lactitol, neotame, ribose, tomatine, polyglycitol, advantum, tagatose, trehalose, glucose, maltose, dextrose, sucrose, fructose, honey, glycyrrhizin, monellin, rabsoside, curculin, corn syrup, lactose, oligosaccharides, and mixtures thereof, and in particular, may be sucralose, aspartame, maltitol, etc., but is not limited thereto.

[0070] In the present invention, preparing the wet granules can be carried out by wet granulation using a binder solution containing any one selected from the group consisting of alcohol, water, and mixtures thereof, and a sweetener. The binder solution can specifically include, but is not limited to, a mixture of alcohol and water, more specifically, an aqueous solution of ethanol, more specifically, an aqueous solution of 58% (w / w) ethanol or an aqueous solution of 50% (w / w) ethanol.

[0071] In the present invention, the binder solution may further contain a binder or an additive capable of imparting binding strength.

[0072] In the present invention, the binder or additive capable of imparting binding power may be any one selected from the group consisting of hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, polyethylene glycol, natural rubber, synthetic rubber, copovidone, ethyl cellulose, methacrylic acid copolymer, and mixtures thereof, or may be hydroxypropyl methylcellulose, but is not limited thereto.

[0073] In the present invention, the wet granulation may be, but is not limited to, high speed shear granulation or fluid bed granulation.

[0074] In the present invention, the pharma- ceutically acceptable excipient may be, but is not limited to, a disintegrant, a diluent, a flavoring agent, a sweetener, a lubricant, or a mixture thereof.

[0075] The disintegrants, diluents, flavoring agents, sweetening agents, lubricants, etc. are the same as those explained in the section on orally disintegrating tablets.

[0076] In the present invention, a sweetener can be used when preparing a wet granule, and may also be added as a pharma- ceutically acceptable additive in the process of preparing the mixture.

[0077] The sweetener used in preparing the wet granules and the sweetener further added in preparing the mixture may be of the same type or of different types.

[0078] In the present invention, the sweetener used in preparing the wet granules may be referred to as the first sweetener, and the sweetener used in preparing the mixture may be referred to as the second sweetener. In this case, "first", "second", etc. are used only to distinguish between multiple components and do not indicate their priority.

[0079] In the present invention, compression into tablets can be carried out by any tabletting method commonly used in the technical field to which the present invention pertains.

[0080] The present invention can provide an orally disintegrating tablet prepared by the above-mentioned preparation method.

[0081] Medical uses of orally disintegrating tablets The present invention can provide a method for preventing or treating a disease mediated by acid pump antagonistic activity, which comprises administering an orally disintegrating tablet.

[0082] The present invention can provide a use of the orally disintegrating tablet for preventing or treating a disease mediated by acid pump antagonist activity.

[0083] The present invention can provide a use of the orally disintegrating tablet in the preparation of a medicament for preventing or treating a disease mediated by acid pump antagonist activity.

[0084] The disease mediated by acid pump antagonist activity may be at least one selected from the group consisting of gastrointestinal disease, gastroesophageal disease, gastroesophageal reflux disease (GERD), peptic ulcer, gastric ulcer, duodenal ulcer, NSAID-induced ulcer, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, non-erosive reflux disease (NERD), visceral referred pain, heartburn, nausea, esophagitis, dysphagia, salivation, airway lesions, and asthma, and may in particular be, but is not limited to, gastroesophageal reflux disease (GERD).

[0085] The contents described in the above section on orally disintegrating tablets can be applied to the medical use of the orally disintegrating tablet of the present invention as long as there is no contradiction. Therefore, the wet granules of the orally disintegrating tablet, the components contained therein, the content of each component, the weight ratio of each component, the uses, the effects, etc. can be applied directly to the medical use of the orally disintegrating tablet of the present invention as long as there is no contradiction. Effect of the Invention

[0086] The orally disintegrating tablet of the present invention disintegrates in the oral cavity in a short time and exhibits excellent sensory properties such as masking the bitter taste, thereby making it possible to significantly improve patient compliance with medication.

[0087] Furthermore, compared with conventional methods in which the bitterness is masked by coating drug particles with polymeric substances or lipid components, or with enteric or gastric bases, the preparation process is simple and economical, and there is no delay in the disintegration and release of the drug, showing a fast disintegration rate and excellent release rate (speed), and producing uniform tablets or small granular particles, thereby improving patient compliance with medication.

[0088] Furthermore, compared to conventional methods that mask bitterness by simply adding high-intensity sweeteners and flavorings in various patterns, the present method does not show any changes in appearance due to moisture or heat (e.g., the appearance of dark brown spots), and therefore has excellent stability in appearance and produces a small total amount of related substances, resulting in excellent stability. [Brief description of the drawings]

[0089] [Figure 1] FIG. 1 shows the drug dissolution rate at pH 1.2 for tablets prepared according to Example 1 and K-CAP tablets. [Diagram 2] FIG. 2 shows the drug dissolution rate at pH 4.0 for the tablets prepared according to Example 1 and K-CAP tablets. [Diagram 3] FIG. 3 is a diagram showing changes in physical properties of tablets prepared according to Example 1 and Comparative Example 1 under stress and accelerated conditions. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0090] The present invention will be described in more detail with reference to the following examples. However, these exemplary embodiments are provided only for the purpose of illustrating the present invention, and therefore the scope of the present invention is not limited thereto. EXAMPLES

[0091] Example 1: Preparation of Tegoprazan Orally Disintegrating Tablet 1 Orally disintegrating tablets were prepared according to the materials and contents described in Example 1 of Table 1 below. Specifically, sucralose, a sweetener, was added to a 58% (w / w) ethanol aqueous solution, and the mixture was stirred for more than 2 hours until completely dissolved to prepare a binder solution. Tegoprazan, the main component, and mannitol 200SD, an excipient, were sieved through a 25 mesh sieve, mixed in a high-speed shear mixer, kneaded with the addition of a binder solution, and granulated. The granulated product was dried and sized in a fluidized bed dryer. Pearitol Flash, Crospovidone CL-SF, Maltitol, Enzyme-modified Stevia, Peppermint Flavor, and Colloidal Silicon Dioxide were added as excipients, disintegrants, sweeteners, and flavorings to the size-adjusted product, and magnesium stearate was further added to mix and lubricate the product. Then, tablet compression was performed by a normal tableting method using a tablet press. Each tablet was prepared to have a weight of 350 mg and a hardness in the range of 5 to 8 kP. EXAMPLES

[0092] Example 2: Preparation of Tegoprazan Orally Disintegrating Tablet 2 Orally disintegrating tablets were prepared according to the materials and contents described in Example 2 in Table 1 below. Specifically, hydroxypropyl methylcellulose (Pharmacoat 603), a binder, was added to a 50% (w / w) ethanol aqueous solution and completely dissolved, and then sucralose, a sweetener, was added, and the binder solution was prepared by stirring for 2 hours or more until completely dissolved. Tegoprazan, the main component, and mannitol 200SD, an excipient, were sieved through a 25-mesh sieve and added to a fluidized bed granulator (GPCG1, manufactured by Glatt), and the binder solution was sprayed to prepare granules, which were then sized and then made into granules. Pearitol flash, crospovidone CL-SF, maltitol, enzyme-modified stevia, peppermint flavor, and colloidal silicon dioxide were added to the product after size adjustment as excipients, disintegrants, sweeteners, and flavorings, and magnesium stearate was further added and mixed to lubricate. Tablet compression was then performed by a normal tableting method using a tablet press. Each tablet weighed 350.5 mg and was prepared to have a hardness in the range of 5 to 8 kP. EXAMPLES

[0093] Example 3: Preparation of Tegoprazan Orally Disintegrating Tablet 3 Orally disintegrating tablets were prepared according to the materials and contents described in Example 3 of Table 1 below. Specifically, maltitol, a sweetener, was added to a 50% (w / w) ethanol aqueous solution, and then the mixture was stirred for 2 hours or more until it was completely dissolved to prepare a binder solution. Tegoprazan, the main component, and mannitol 200SD, an excipient, were sieved through a 25 mesh sieve, mixed in a high-speed shear mixer, and the binder solution was added and kneaded to granulate. The granules were dried in a fluidized bed dryer and particle size adjustment was performed. Pearitol flash, crospovidone CL-SF, maltitol, enzyme-modified stevia, peppermint flavor, and colloidal silicon dioxide were added as excipients, disintegrants, sweeteners, and flavorings to the size-adjusted product, and magnesium stearate was added and mixed to lubricate it. Then, tablet compression was performed by a normal tableting method using a tablet press. Each tablet was prepared to have a weight of 350 mg and a hardness in the range of 5 to 8 kP. EXAMPLES

[0094] Example 4: Preparation of Tegoprazan Orally Disintegrating Tablet 4 Orally disintegrating tablets were prepared according to the materials and contents described in Example 4 of Table 1 below. Specifically, aspartame, a sweetener, was added to a 50% (w / w) ethanol aqueous solution, and then the mixture was stirred for 2 hours or more until it was completely dissolved to prepare a binder solution. Tegoprazan, the main component, and mannitol 200SD, an excipient, were sieved through a 25 mesh sieve, mixed in a high-speed shear mixer, and the binder solution was added and kneaded to granulate. The granules were dried in a fluidized bed dryer and particle size adjustment was performed. Pearitol Flash, Crospovidone CL-SF, Maltitol, Enzyme-modified Stevia, Peppermint Flavor, and Colloidal Silicon Dioxide were added as excipients, disintegrants, sweeteners, and flavorings to the size-adjusted product, and magnesium stearate was added and mixed to lubricate it. Then, tablet compression was performed by a normal tableting method using a tablet press. Each tablet was prepared to have a weight of 350 mg and a hardness in the range of 5 to 8 kP. EXAMPLES

[0095] Example 5: Preparation of Tegoprazan Orally Disintegrating Tablet 5 Orally disintegrating tablets were prepared according to the materials and contents described in Example 5 of Table 1 below. Specifically, sucralose, a sweetener, was added to a 50% (w / w) aqueous solution of ethanol, and then the mixture was stirred for 2 hours or more until it was completely dissolved to prepare a binder solution. Tegoprazan, the main component, and xylitol, an excipient, were sieved through a 25-mesh sieve, mixed in a high-speed shear mixer, kneaded with the binder solution, and granulated. The granulated product was dried in a fluidized bed dryer and subjected to particle size adjustment. Pearitol flash, crospovidone CL-SF, maltitol, enzyme-modified stevia, peppermint flavor, and colloidal silicon dioxide were added as excipients, disintegrants, sweeteners, and flavorings to the size-adjusted product, and magnesium stearate was added and mixed to lubricate it. Then, tablet compression was performed by a normal tableting method using a tablet press. Each tablet was prepared to have a weight of 350 mg and a hardness in the range of 5 to 8 kP.

[0096] Comparative Example 1. Preparation of Tegoprazan Orally Disintegrating Tablet 6 Orally disintegrating tablets were prepared according to the materials and details described in Comparative Example 1 in Table 1 below. Specifically, all of the materials described in Comparative Example 1 in Table 1 were sieved through a 25 mesh sieve, mixed, and compressed into tablets by a normal tableting method using a tablet press. Each tablet was prepared to have a weight of 350 mg and a hardness in the range of 5 to 8 kP.

[0097] [Table 1]

[0098] Experimental Example 1: Evaluation of disintegration time Orally disintegrating tablets need to be administered while disintegrating in the oral cavity, and therefore they are required to disintegrate quickly. Therefore, the disintegration times of the tablets prepared according to Examples 1 to 5 and Comparative Example 1 were measured.

[0099] In the in vitro disintegration experiment, a 90 mm diameter filter paper (see WH1442090) was placed on a petri dish (100 × 10 mm), and 10 mL of a 10% aqueous solution of cobalt (II) chloride hexahydrate was completely soaked into the petri dish. Then, a tablet was placed on the filter paper, and the time it took for the water to reach the edge of the tablet by capillary action was measured by visually checking the color change (measurements were performed three times).

[0100] In the in vivo disintegration experiment, 10 subjects ingested the tablets without water, and the time it took for the tablets to completely disintegrate in the oral cavity due to saliva was measured.

[0101] The disintegration test using a disintegration tester was performed according to the disintegration test method of the Korean Pharmacopoeia General Test Method (n=6).

[0102] The average values ​​for each test are shown in Table 2 below.

[0103] [Table 2]

[0104] As a result, it was confirmed that the tablets prepared according to Examples 1 to 5 and Comparative Example 1 rapidly disintegrated within 30 seconds in all of the in vitro disintegration experiment, the in vivo disintegration experiment, and the disintegration experiment using a disintegration tester.

[0105] Experimental example 2: Sensory evaluation The tablets prepared according to the above Examples 1 to 5 and Comparative Example 1 were administered to 10 subjects without water, and then sensory evaluation (evaluation of irritation and bitterness) was performed. Each subject recorded a score (0 to 5 points) for irritation and bitterness, and the obtained scores were averaged and are shown in Table 3 below.

[0106] [Table 3]

[0107] As a result, it was confirmed that Comparative Example 1, which was prepared by direct compression in which a sweetener was added in powder form, had a very strong bitter taste and a strong unpleasant sensation in the mouth.On the other hand, Examples 1 and 3 to 5, which were prepared by high-speed shear granulation, and Example 2, which was prepared by fluidized bed granulation, had very little bitterness and a smooth disintegration sensation in the mouth because the binder solution containing the sweetener adhered to and coated the particles of tegoprazan and excipients, and therefore were confirmed to have a bitterness-reducing effect as well as excellent sensory properties.

[0108] Experimental Example 3: Dissolution Rate Evaluation The drug dissolution rates of the tablets prepared according to Example 1 above and 50 mg K-CAP tablets from HK Innoen Co., Ltd. were compared based on Chapter 3 Comparative Dissolution Tests in the Pharmaceutical Equivalence Testing Standards. At the start of the test, samples were taken at 0, 5, 10, 15, and 30 minutes from the pH 1.2 dissolution test solution, and at 0, 5, 10, 15, 30, 45, 60, 90, and 120 minutes from the pH 4.0 dissolution test solution, and were subjected to liquid chromatography under the following conditions. The dissolution rates of tegoprazan were then calculated and shown in Table 4 and Figures 1 and 2 below.

[0109] <Dissolution conditions> Rotational speed: 50 rpm Test volume: 900 mL Test liquid temperature: 37±0.5℃ Test solutions: Korean Pharmacopoeia pH 1.2 and pH 4.0 solutions <Liquid chromatography conditions> Column: A stainless steel tube with an inner diameter of approximately 4.6 mm and a length of 15 cm packed with octadecyl silica gel for liquid chromatography with a particle size of 5 μm. Column temperature: constant temperature around 30℃ Sample injection volume: 10μL Mobile phase: 0.01 mol / L ammonium acetate buffer:ACN=11:9 ·Flow rate: 1.0 mL / min Detector: UV spectrophotometer (measurement wavelength 262 nm)

[0110] [Table 4]

[0111] As a result, it was confirmed that the tablets prepared according to Example 1 exhibited an excellent dissolution rate comparable to that of the control drug, K-CAP tablets, without causing any delay in the release of tegoprazan.

[0112] Experimental Example 4: Stability evaluation In order to evaluate the stability under stress conditions and accelerated conditions in Example 1 and Comparative Example 1, stability tests were conducted under stress conditions (60°C, 80% RH) and accelerated conditions (40°C, 75% RH) in HDPE bottles and PTP (aluminum) packaging materials, and the total amount of related substances and the changes in appearance are shown in Table 6 below and Figure 3, respectively.

[0113] <Liquid chromatography conditions> Column: A stainless steel tube with an inner diameter of approximately 4.6 mm and a length of 15 cm packed with octadecyl silica gel for liquid chromatography with a particle size of 2.7 μm. Column temperature: constant temperature around 30℃ Sample injection volume: 10μL Mobile phase A: 0.01 mol / L ammonium acetate buffer:ACN=19:1 Mobile phase B: ACN ·Flow rate: 0.8 mL / min Detector: UV spectrophotometer (measurement wavelength 220 nm)

[0114] [Table 5]

[0115] [Table 6]

[0116] As a result, the tablets prepared according to Example 1 produced less total amount of related substances under stress conditions and accelerated conditions compared to the tablets prepared according to Comparative Example 1 (Table 6), and the tablets of Comparative Example 1 produced dark brown spots on the tablet surface under stress conditions and accelerated conditions, whereas the tablets prepared according to Example 1 showed no change in appearance under stress conditions and accelerated conditions (Figure 3), thereby confirming that they exhibit excellent stability.

[0117] Experimental Example 5: Evaluation of stability according to type and weight ratio of sweetener In order to evaluate the stability under stress conditions depending on the type of sweetener contained in the granules and the weight ratio of tegoprazan to sweetener in the granules, orally disintegrating tablets were prepared according to the materials and contents listed in Table 7 below (Examples 6 to 10 and Comparative Example 2 were prepared in the same manner as Example 1), and a stability test was performed under stress conditions (60°C, 80% RH).

[0118] The total amount of related substances is given in Table 8 below.

[0119] [Table 7]

[0120] [Table 8]

[0121] As a result, it was confirmed that the tablets of Examples 6 to 10, in which the weight ratio of tegoprazan to sweetener was 1:0.05 to 1:0.2, produced less total amount of related substances than the tablet of Comparative Example 2, in which the weight ratio of tegoprazan to sweetener was 1:0.5, and therefore exhibited superior stability.

[0122] On the other hand, when broken down by type of sweetener, the tablets of Example 8 containing sucralose, the tablets of Example 9 containing aspartame, and the tablets of Example 10 containing maltitol all produced small amounts of related substances, confirming that they exhibit excellent stability regardless of the type of sweetener.

[0123] Although certain parts of the present invention have been described in detail above, it is clear to those skilled in the art that such detailed description is provided only to describe exemplary embodiments and is not to be construed as limiting the scope of the present invention. Therefore, it should be understood that the substantial scope of the present invention is defined by the appended claims and their equivalents. Below are [1] to

[34] which correspond to claims 1 to 34 of the original application. [1] An orally disintegrating tablet comprising moist granules comprising a compound represented by the following formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener. [ka] [2] The orally disintegrating tablet according to [1], wherein the moist granules contain a compound represented by formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener in a weight ratio of 1:0.001 to 1:0.4. [3] The orally disintegrating tablet according to [2], wherein the moist granules contain the compound represented by formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener in a weight ratio of 1:0.05 to 1:0.2. [4] The orally disintegrating tablet of claim 1, wherein the sweetening agent is one selected from the group consisting of sucralose, aspartame, saccharin, acesulfame potassium, stevioside, enzyme-modified stevia, sucrose, isomalt, maltitol, mannitol, sorbitol, steviol glycosides, erythritol, xylose, xylitol, lactitol, neotame, ribose, tomatine, polyglycitol, advantum, tagatose, trehalose, glucose, maltose, dextrose, sucrose, fructose, honey, glycyrrhizin, monellin, rabsoside, curculin, corn syrup, lactose, oligosaccharides, and mixtures thereof. [5] The orally disintegrating tablet according to [1], containing a sweetener in an amount of 0.01 to 10% by weight based on the total weight of the tablet. [6] The orally disintegrating tablet according to [1], further comprising a disintegrant. [7] The orally disintegrating tablet according to [6], wherein the disintegrant is one selected from the group consisting of crospovidone, croscarmellose sodium, sodium starch glycolate, alginic acid, sodium alginate, low-substituted hydroxypropylcellulose, carboxymethylcellulose, corn starch, pregelatinized starch, microcrystalline cellulose, hydroxypropylcellulose, sodium bicarbonate, and mixtures thereof. [8] The orally disintegrating tablet according to [6], wherein the disintegrant is contained in an amount of 1 to 50% by weight based on the total weight of the tablet. [9] The orally disintegrating tablet according to [1], further comprising a diluent, a flavoring agent, a sweetener, a lubricant, or a mixture thereof.

[10] The orally disintegrating tablet according to [9], wherein the diluent is one selected from the group consisting of mannitol, lactose, starch, microcrystalline cellulose, Ludipress, Pearylitol Flash, dibasic calcium phosphate, dextrose, maltose, erythritol, sucrose, maltitol, trehalose, glucose, xylitol, F-Melt, sorbitol, pregelatinized starch, anhydrous dibasic calcium phosphate, dicalcium phosphate, and mixtures thereof.

[11] The orally disintegrating tablet according to [9], containing a diluent in an amount of 1 to 99% by weight based on the total weight of the tablet.

[12] The orally disintegrating tablet according to [9], wherein the flavoring agent is one selected from the group consisting of peppermint flavor, yogurt flavor, fruit flavor, and mixtures thereof.

[13] The orally disintegrating tablet according to [9], containing a flavoring agent in an amount of 0.01 to 10% by weight based on the total weight of the tablet.

[14] The orally disintegrating tablet according to [9], wherein the lubricant is one selected from the group consisting of stearic acid, metal stearates, talc, colloidal silica, sucrose fatty acid esters, hydrogenated vegetable oils, waxes, glycerin fatty acid esters, glycerol dibehenate, and mixtures thereof.

[15] The orally disintegrating tablet according to [9], containing a lubricant in an amount of 0.1 to 10% by weight based on the total weight of the tablet.

[16] The orally disintegrating tablet according to [1], wherein the wet granules are prepared using a binder solution comprising one selected from the group consisting of alcohol, water and mixtures thereof, and a sweetener.

[17] The orally disintegrating tablet according to

[16] , wherein the binder solution further contains a binder or an additive capable of imparting binding strength.

[18] The orally disintegrating tablet according to

[17] , wherein the binder or additive capable of imparting binding strength is one selected from the group consisting of hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, polyethylene glycol, natural rubber, synthetic rubber, copovidone, ethyl cellulose, methacrylic acid copolymer, and mixtures thereof.

[19] The orally disintegrating tablet according to [1], wherein the wet granules are prepared by high shear granulation or fluid bed granulation.

[20] The orally disintegrating tablet according to [1], which disintegrates within 30 seconds.

[21] The orally disintegrating tablet according to [1], wherein the bitterness of the orally disintegrating tablet is masked.

[22] The orally disintegrating tablet according to [1], wherein the orally disintegrating tablet is used for the prevention or treatment of a disease mediated by acid pump antagonism.

[23] The orally disintegrating tablet according to

[22] , wherein the disease mediated by acid pump antagonism is at least one selected from the group consisting of gastrointestinal disease, gastroesophageal disease, gastroesophageal reflux disease (GERD), peptic ulcer, gastric ulcer, duodenal ulcer, NSAID-induced ulcer, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, non-erosive reflux disease (NERD), visceral referred pain, heartburn, nausea, esophagitis, dysphagia, salivation, airway lesions, and asthma.

[24] A method for preparing an orally disintegrating tablet, comprising: (1) preparing a wet granule comprising a compound represented by the following formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener; (2) preparing a mixture by adding one or more pharma- ceutically acceptable excipients to the wet granules; and (3) compressing the mixture into tablets; The method includes: [ka]

[25] The method according to

[24] , wherein the sweetening agent is one selected from the group consisting of sucralose, aspartame, saccharin, acesulfame potassium, stevioside, enzyme-modified stevia, sucrose, isomalt, maltitol, mannitol, sorbitol, steviol glycoside, erythritol, xylose, xylitol, lactitol, neotame, ribose, tomatine, polyglycitol, advantum, tagatose, trehalose, glucose, maltose, dextrose, sucrose, fructose, honey, glycyrrhizin, monellin, rabsoside, curculin, corn syrup, lactose, oligosaccharides, and mixtures thereof.

[26] The method according to

[24] , wherein the preparation of the wet granules is carried out by wet granulation with a binder solution comprising one selected from the group consisting of alcohol, water, and mixtures thereof, and a sweetener.

[27] The method of

[26] , wherein the binder solution further comprises an additive capable of imparting a binder or binding strength.

[28] The method according to

[27] , wherein the binder or additive capable of imparting binding strength is one selected from the group consisting of hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, polyethylene glycol, natural rubber, synthetic rubber, copovidone, ethyl cellulose, methacrylic acid copolymer, and mixtures thereof.

[29] The method according to

[26] , wherein the wet granulation is high shear granulation or fluid bed granulation.

[30] The method according to

[24] , wherein the pharma- ceutically acceptable excipient is a disintegrant, a diluent, a flavoring agent, a sweetener, a lubricant, or a mixture thereof.

[31] An orally disintegrating tablet prepared by the preparation method described in any one of

[24] to

[30] .

[32] A method for preventing or treating a disease mediated by acid pump antagonism, comprising administering the orally disintegrating tablet according to any one of [1] to

[23] .

[33] Use of the orally disintegrating tablet according to any one of [1] to

[23] for the prevention or treatment of a disease mediated by acid pump antagonism.

[34] Use of the orally disintegrating tablet according to any one of [1] to

[23] in the preparation of a preventive or therapeutic agent for a disease mediated by acid pump antagonism.

Claims

1. An orally disintegrating tablet comprising moist granules comprising a compound represented by the following formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener. 【Chemistry 1】

2. 2. The orally disintegrating tablet according to claim 1, wherein the wet granules contain the compound represented by formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener in a weight ratio of 1:0.001 to 1:0.

4.

3. 3. The orally disintegrating tablet according to claim 2, wherein the wet granules contain the compound represented by formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener in a weight ratio of 1:0.05 to 1:0.

2.

4. 2. The orally disintegrating tablet of claim 1, wherein the sweetener is one selected from the group consisting of sucralose, aspartame, saccharin, acesulfame potassium, stevioside, enzyme-modified stevia, sucrose, isomalt, maltitol, mannitol, sorbitol, steviol glycoside, erythritol, xylose, xylitol, lactitol, neotame, ribose, tomatine, polyglycitol, advantum, tagatose, trehalose, glucose, maltose, dextrose, sucrose, fructose, honey, glycyrrhizin, monellin, rabsoside, curculin, corn syrup, lactose, oligosaccharides, and mixtures thereof.

5. 2. The orally disintegrating tablet according to claim 1, comprising a sweetener in an amount of 0.01 to 10% by weight based on the total weight of the tablet.

6. The orally disintegrating tablet according to claim 1 , further comprising a disintegrant.

7. 7. The orally disintegrating tablet according to claim 6, wherein the disintegrant is one selected from the group consisting of crospovidone, croscarmellose sodium, sodium starch glycolate, alginic acid, sodium alginate, low-substituted hydroxypropylcellulose, carboxymethylcellulose, corn starch, pregelatinized starch, microcrystalline cellulose, hydroxypropylcellulose, sodium bicarbonate, and mixtures thereof.

8. 7. The orally disintegrating tablet according to claim 6, comprising a disintegrant in an amount of 1 to 50% by weight based on the total weight of the tablet.

9. 10. The orally disintegrating tablet of claim 1, further comprising a diluent, a flavoring agent, a sweetener, a lubricant, or a mixture thereof.

10. 10. The orally disintegrating tablet according to claim 9, wherein the diluent is one selected from the group consisting of mannitol, lactose, starch, microcrystalline cellulose, ludipress, peritol flash, dibasic calcium phosphate, dextrose, maltose, erythritol, sucrose, maltitol, trehalose, glucose, xylitol, F-melt, sorbitol, pregelatinized starch, anhydrous dibasic calcium phosphate, dicalcium phosphate, and mixtures thereof.

11. 10. The orally disintegrating tablet according to claim 9, comprising a diluent in an amount of 1 to 99% by weight based on the total weight of the tablet.

12. 10. The orally disintegrating tablet according to claim 9, wherein the flavoring agent is one selected from the group consisting of peppermint flavor, yogurt flavor, fruit flavor, and mixtures thereof.

13. 10. The orally disintegrating tablet according to claim 9, comprising a flavoring agent in an amount of 0.01 to 10% by weight based on the total weight of the tablet.

14. 10. The orally disintegrating tablet according to claim 9, wherein the lubricant is one selected from the group consisting of stearic acid, metal stearates, talc, colloidal silica, sucrose fatty acid esters, hydrogenated vegetable oils, waxes, glycerin fatty acid esters, glycerol dibehenate, and mixtures thereof.

15. 10. The orally disintegrating tablet according to claim 9, comprising a lubricant in an amount of 0.1 to 10% by weight based on the total weight of the tablet.

16. 2. The orally disintegrating tablet of claim 1, wherein the wet granules are prepared using a binder solution comprising one selected from the group consisting of alcohol, water and mixtures thereof and a sweetener.

17. 17. The orally disintegrating tablet according to claim 16, wherein the binder solution further comprises a binder or an additive capable of imparting binding strength.

18. 18. The orally disintegrating tablet according to claim 17, wherein the binder or additive capable of imparting binding power is one selected from the group consisting of hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, polyethylene glycol, natural rubber, synthetic rubber, copovidone, ethyl cellulose, methacrylic acid copolymer, and mixtures thereof.

19. 2. The orally disintegrating tablet of claim 1, wherein the wet granules are prepared by high shear granulation or fluid bed granulation.

20. 2. The orally disintegrating tablet according to claim 1, which disintegrates within 30 seconds.

21. 2. The orally disintegrating tablet according to claim 1, wherein the bitterness of the orally disintegrating tablet is masked.

22. The orally disintegrating tablet according to claim 1, which is used for the prevention or treatment of a disease mediated by acid pump antagonism.

23. The orally disintegrating tablet according to claim 22, wherein the disease mediated by acid pump antagonism is at least one selected from the group consisting of gastrointestinal disease, gastroesophageal disease, gastroesophageal reflux disease (GERD), peptic ulcer, gastric ulcer, duodenal ulcer, NSAID-induced ulcer, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, non-erosive reflux disease (NERD), visceral referred pain, heartburn, nausea, esophagitis, dysphagia, salivation, airway lesions, and asthma.

24. 1. A method for preparing an orally disintegrating tablet, comprising: (1) preparing a wet granule comprising a compound represented by the following formula 1, a pharma- ceutically acceptable salt thereof, a hydrate or solvate thereof, or a mixture thereof, and a sweetener; (2) preparing a mixture by adding one or more pharma- ceutically acceptable excipients to the wet granules; and (3) compressing the mixture into tablets; The method includes: 【Chemistry 2】

25. 25. The method of claim 24, wherein the sweetening agent is one selected from the group consisting of sucralose, aspartame, saccharin, acesulfame potassium, stevioside, enzyme-modified stevia, sucrose, isomalt, maltitol, mannitol, sorbitol, steviol glycoside, erythritol, xylose, xylitol, lactitol, neotame, ribose, tomatine, polyglycitol, advantum, tagatose, trehalose, glucose, maltose, dextrose, sucrose, fructose, honey, glycyrrhizin, monellin, rabsoside, curculin, corn syrup, lactose, oligosaccharides, and mixtures thereof.

26. 25. The method of claim 24, wherein the preparation of the wet granules is carried out by wet granulation with a binder solution comprising one selected from the group consisting of alcohol, water, and mixtures thereof, and a sweetener.

27. 27. The method of claim 26, wherein the binder solution further comprises a binder or additive capable of imparting cohesive strength.

28. 28. The method of claim 27, wherein the binder or additive capable of imparting cohesive strength is one selected from the group consisting of hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, polyethylene glycol, natural gum, synthetic gum, copovidone, ethyl cellulose, methacrylic acid copolymers, and mixtures thereof.

29. 27. The method of claim 26, wherein the wet granulation is high shear granulation or fluid bed granulation.

30. 25. The method of claim 24, wherein the pharma- ceutically acceptable excipient is a disintegrant, a diluent, a flavoring agent, a sweetening agent, a lubricant, or a mixture thereof.

31. An orally disintegrating tablet prepared by the method according to any one of claims 24 to 30.

32. A method for preventing or treating a disease mediated by acid pump antagonism, comprising administering the orally disintegrating tablet according to any one of claims 1 to 23.

33. Use of the orally disintegrating tablet according to any one of claims 1 to 23 for the prevention or treatment of a disease mediated by acid pump antagonism.

34. Use of the orally disintegrating tablet according to any one of claims 1 to 23 in the preparation of a preventive or therapeutic agent for a disease mediated by acid pump antagonism.

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