JPWO1995020380A1 - Orally dissolving compression molded product and its manufacturing method - Google Patents

Abstract

(57) [Abstract] The present invention provides an orally dissolving compression-molded product obtained by granulating a sugar with low moldability with a sugar with high moldability. It exhibits rapid disintegration and solubility in the oral cavity and moderate hardness.

Description

[Detailed Description of the Invention] Oral Dissolving Compression Molded Product and Its Manufacturing Method Technical Field The present invention relates to an oral dissolving compression molded product that exhibits rapid disintegration and solubility in the oral cavity and appropriate hardness, and a manufacturing method thereof. Preferably, the present invention relates to an oral dissolving compression molded product useful in the pharmaceutical field.

An orally dissolving compression-molded product is a compression-molded product that has practically sufficient disintegrability and solubility in saliva when simply held in the mouth without the need for water, and that has appropriate hardness. Here, practically sufficient disintegrability and solubility means that the product disintegrates or dissolves in the oral cavity within approximately 1 to 120 seconds, preferably 1 to 60 seconds, and more preferably 1 to 40 seconds. Appropriate hardness means that the molded product has sufficient strength to withstand breakage during the manufacturing and distribution processes.

BACKGROUND ART While various oral pharmaceutical dosage forms are known, few are designed to be easy for patients to take. Therefore, there is a need for the development of easy-to-use dosage forms, particularly for elderly people and children, who often have difficulty taking medications.

For example, tablets and capsules, which are commonly used as oral preparations, are often difficult for elderly people and children with weak swallowing abilities to swallow, or they can get stuck in the pharynx or esophagus, so many patients are reluctant to take them. Chewable tablets are not suitable for elderly people and children with weak chewing abilities.

Powders and granules remain in the mouth, making them difficult to swallow and leaving a feeling of discomfort in the mouth. Elderly people may choke when taking them, or the granules may get stuck between dentures, causing pain and discomfort. Furthermore, powders and granules require the patient to tear the pouch to place the medication in their mouth, but tearing the pouch can be difficult for elderly people and children, and some of the medication may be spilled.

These oral medications require water when taken, and elderly people and children often require large amounts of water due to the difficulty of administering them. However, some patients may wish to limit their fluid intake, especially before bedtime, due to issues with nocturnal urination. Furthermore, for patients who need to take these medications regularly while carrying out their daily activities, it can be difficult to always have water available, depending on the situation, which often leads to poor medication compliance.

Syrups and other formulations are preferred for elderly people and children, but measuring and administering them can be difficult for these individuals, making it difficult to ensure that they receive the correct amount. Many elderly people also have difficulty even bringing liquid medication to their mouths. Considering the hassle of administering syrups, these formulations are not necessarily suitable for elderly people or children, unless a caregiver is involved.

In consideration of these circumstances, efforts have been made to develop orally dissolving formulations suitable for use by elderly people and children, as described below. However, various problems have arisen, such as the complexity of the manufacturing process, the need for new capital investment for manufacturing, limitations on the range of active ingredients, and the lack of appropriate hardness in the formulation due to the excessive pursuit of rapid disintegration and solubility in the oral cavity, making them difficult to handle, making them insufficient for practical use.

As we move toward an aging society, the elderly are more likely to suffer from chronic diseases and tend to take medications for long periods of time. Given this, the development of practical formulations suitable for elderly people is an urgent priority. Furthermore, in order to ensure quality of life, it is desirable to develop practical formulations that are easy to swallow and handle, tailored to the patient's abilities and living situation.

For example, Japanese Patent Publication No. 58-24410 describes a method for producing porous tablets with good disintegratability by mixing the tablet contents with a solvent that is inert to the tablet contents and freezes at temperatures between -30°C and +25°C, with the solvent being 5 to 80% by weight of the total mixture, solidifying the mixture by placing it in an inert cooling medium, compressing it at a temperature below the freezing point of the solvent to form tablets, and then evaporating the solvent by freeze-drying or natural drying.

Japanese Patent Application Laid-Open No. 3-86837 describes a readily dissolvable carrier material with sufficient strength that can be obtained by contacting a composition comprising a water-soluble, hydratable gel or foam material with an anhydrous organic liquid desiccant, such as absolute ethanol, at a temperature of about 0°C or below until substantially all of the water is removed.

However, both manufacturing methods require complex processes and require equipment such as freeze-drying, which increases costs.

Japanese Patent Application Laid-Open No. 2-32014 describes a solid preparation in the form of a moistened tablet suitable for oral administration. However, this method involves preparing a moistened mass with ethanol/water or water alone, placing it in a mold, and drying it to obtain tablets. This method, unlike conventional manufacturing methods, is not sufficiently productive.

Japanese Patent Publication No. 61-15830 describes an antacid composition having a porous, ultrafine crystalline structure, comprising an antacid and a confectionery base material containing a confectionery sweetener and a plasticizer. Japanese Patent Publication No. 3-209336 describes a pharmaceutical composition comprising particles of at least one pharmaceutically active compound uniformly dispersed within a crystalline matrix of a crystalline sugar alcohol derived from at least one monosaccharide or polysaccharide. However, because both compositions require melting the sugar component at temperatures above 100°C, the range of application of the active agent is limited due to thermal stability.

Furthermore, R. P. Scherer has commercialized an orally soluble formulation under the trade name "Zydis." However, because it is prepared by freeze-drying, it requires freeze-drying equipment and takes a long time to manufacture, resulting in high costs. Furthermore, freeze-dried formulations have low strength and require special handling precautions, making them unsatisfactory for elderly patients. For example, they cannot be easily pushed out of the container (PTP: Press-Through Package) like regular tablets.

Orally soluble formulations produced by the freeze-drying method (hereafter referred to as freeze-dried formulations) are particularly excellent in terms of disintegration and solubility. However, because the formulations lack sufficient hardness to withstand destruction during the manufacturing and distribution processes, they lack sufficient shelf life.

In addition, oral dissolving formulations have been reported that are manufactured by tableting rather than the conventional freeze-drying method.

Japanese Patent Application Laid-Open No. 5-271054 discloses that when a mixture containing a medicinal ingredient, sugars, and enough water to moisten the surface of the sugar particles is compressed into tablets and then dried, an orally dissolving tablet having an appropriate strength and a porous structure that disintegrates and dissolves rapidly in the mouth is obtained.

However, orally dissolving formulations produced by the above-mentioned tableting method (hereinafter referred to as tableted formulations) do not require the manufacturing process required for lyophilized formulations, and furthermore, the formulations have good shelf life because they have an appropriate hardness that prevents the dosage form from breaking down during distribution. However, because their production involves simply tableting a mixture or compound, there remains room for further study regarding the rapid disintegration and dissolution characteristics of orally dissolving formulations in the oral cavity.

Furthermore, the following patents focus on the moldability and direct tableting of sugar.

Japanese Patent Publication No. 5-310558 discloses that blending sorbitol powder with a bulk density of less than 60 g/100 ml with mannitol or lactose, which have poor binding and compactibility, allows for the reduction of the amount of other highly compactible additives, such as cellulose compounds, acrylic acid compounds, and gelatin, resulting in a solid formulation with excellent disintegration properties. Similarly, Japanese Patent Publication No. 59-118058 and German Patent Publication No. 1617638 are known to use sorbitol with a specific bulk density. While these patents suggest that sorbitol with a specific bulk density can be used as a binder for direct compression, the purpose of these patents is to manufacture additives for direct compression, and they relate to the manufacture of additives and tablets that can produce tablets with higher hardness at normal tableting pressures.

In Japanese Patent Application Laid-Open No. 5-170669, the moldability of lactose is improved by adding a sugar alcohol to lactose with a high β-lactose content and then drying the resulting aqueous solution by roller drying. However, these methods use special sugars and are not simple, inexpensive, or practical.

U.S. Patent No. 4,698,101 describes an invention relating to a fructose-based formulation aid that can be directly compressed into tablets by granulating fructose with an aqueous maltose solution.

JP 4-505918 A discloses an invention relating to a fructose-based formulation aid that can be directly compressed into tablets by granulating fructose with an aqueous polyol solution of sorbitol, maltitol, lactitol, xylitol, mannitol, isomaltol, or a mixture thereof.

Although these patents use fructose as a granule core, they relate to conventional tablets, not orally dissolving tablets. Furthermore, due to the high hygroscopicity of fructose, the granules absorb moisture with normal handling, resulting in insufficient fluidity and potential tableting problems.

The objectives of the present invention are to provide an orally dissolving compression-molded product that exhibits rapid disintegration and dissolution in the oral cavity and an appropriate hardness to prevent breakage; to provide a manufacturing method for obtaining the orally dissolving compression-molded product using a conventional manufacturing process; to provide an orally dissolving compression-molded product that is easy to take without water and a manufacturing method therefor; and to provide a useful orally dissolving compression-molded product that is highly industrially productive, has a uniform active ingredient content, and is a consistent dosage form.

DISCLOSURE OF THE INVENTION Generally, compressed products (such as tablets) have an appropriate hardness for their intended purpose. However, because they are intended to disintegrate and dissolve in the digestive tract upon oral administration, allowing the active ingredient to be absorbed, they do not take into consideration rapid disintegration and solubility in the oral cavity.

Therefore, the disintegration and solubility in the oral cavity were insufficient, and the tablets did not simultaneously exhibit rapid disintegration and solubility.

To solve the above problems, the materials used to make the orally dissolving compression-molded products must simultaneously possess the following properties: a rapid dissolution rate in the mouth when compressed, e.g., when formed into tablets, and high moldability to achieve the appropriate hardness.

First, the inventors focused on sugars as a material for intraoral compression molding and conducted research.

The study involved measuring the oral dissolution time and hardness of tablets made from various sugars that are normally used as additives such as excipients in pharmaceutical preparations, compressed at a compression pressure of 10 to 50 kg/cm ² .

The results showed that no material possessed both of these properties simultaneously. However, unexpectedly, we gained the new knowledge that sugars can be classified into two types: sugars that dissolve quickly in the mouth when tableted, and sugars that are easily molded to achieve hardness.

However, it has not been possible to simultaneously achieve the appropriate hardness after compression molding and the rapid disintegration and dissolution in the mouth using either low-moldability or high-moldability sugars alone.

In this case, sugars with low moldability, although inferior in moldability, showed a very fast dissolution rate in the oral cavity of within about 15 seconds when tableted, but did not achieve sufficient hardness. For example, when 150 mg of sugars with low moldability were molded using a punch with a diameter (φ) of 8 mm at a tableting pressure of 50 kg/ ^cm2 , sufficient tablet strength was not obtained.

Furthermore, although sugars with high moldability naturally have good moldability, their disintegration in the mouth is inferior to sugars with low moldability.

For example, when 150 mg of a highly moldable saccharide was molded using a punch with a diameter (φ) of 8 mm at a tableting pressure of 50 kg/ ^cm² , sufficient tablet strength was obtained, but rapid disintegration and dissolution in the oral cavity were not achieved.

Furthermore, even when a saccharide with low moldability and a saccharide with high moldability were simply mixed (physical mixing) and tableted, rapid disintegration and solubility in the oral cavity were not obtained. For example, when 189 g of lactose, 10 g of maltitol, and 1 g of magnesium stearate were mixed and the mixture was compressed into tablets of 300 mg each, using a rotary tableting machine with a pestle of φ10 mm and 10 mmR at a pressure of 441 kg/ ^cm2 , rapid disintegration and solubility in the oral cavity were not obtained.

Next, the inventors investigated various methods for simultaneously achieving both high moldability and appropriate hardness during compression molding while maintaining the fast dissolution rate of low-moldability sugars. They focused on combinations of soluble, low-moldability sugars with highly moldable sugars, including blending ratios and blending methods. As a result, they were able to overcome the drawbacks of both low-moldability and highly moldable sugars by granulating a sugar with high moldability sugars, which have poor moldability but excellent disintegration and solubility. Using this material, they were able to obtain a material that was suitable for both low-moldability and highly moldable sugars. Compressed products obtained using this material through a standard compression molding process, such as tableting, had appropriate hardness and exhibited rapid disintegration and dissolution when placed in the mouth.

In order to solve the above-mentioned problems, the inventors conducted extensive research into orally dissolving compression-molded products. As a result, they discovered that a molded product obtained through a conventional manufacturing process from a material made by granulating a low-moldability sugar with a high-moldability sugar, which has rapid disintegration and solubility, exhibits rapid disintegration and solubility in the oral cavity simply by placing it in the mouth, and has an appropriate hardness that prevents the dosage form from breaking down during the manufacturing and flow processes, thereby completing the present invention.

Furthermore, the present invention uses a highly moldable sugar as a binder during granulation, rather than the conventionally used water-soluble polymers, such as hydroxypropyl cellulose (HPC) or hydroxypropylmethyl cellulose (HPMC), resulting in a formulation that is completely different in composition and shape from existing orally dissolving formulations.

Furthermore, we have discovered that granulating a sugar with low moldability with a sugar with high moldability can produce a material for an orally dissolving compression-molded product, preferably an orally dissolving tablet, and have completed the present invention.

That is, the present invention provides an orally dissolving compression-molded product that is made from a saccharide having low moldability and a saccharide having high moldability and that has rapid disintegration and dissolution properties in the oral cavity.

The "sugar with low moldability", which is one of the constituent elements of the present invention, generally means a sugar that exhibits a hardness of 0 to 2 kg when 150 mg of the sugar is tableted using a punch with a diameter (φ) of 8 mm at a tableting pressure of 10 to 50 kg/ ^cm² , and examples thereof include lactose, mannitol, glucose, sucrose, xylitol, etc. Preferably, lactose or mannitol is used.

These sugars may be used alone or in combination of two or more.

The term "sugars with high moldability" generally refers to sugars that exhibit a hardness of 2 kg or more when 150 mg of the sugar is tableted using a punch with a diameter (φ) of 8 mm at a tableting pressure of 10 to 50 kg/ ^cm² , and includes, for example, maltose, maltitol, sorbitol, and oligosaccharides. Maltose and maltitol are preferred.

The oligosaccharides used in the present invention are not particularly limited as long as they are disaccharides or greater that rapidly dissolve in the oral cavity. Oligosaccharides consisting of disaccharides to hexasaccharides are preferred. Oligosaccharides are not limited by the type or combination of constituent monosaccharides. Examples include lactose-fructose (e.g., product name: Nyuka Oligo LS-55P, Hayashibara Shoji Co., Ltd.). Oligosaccharides are sometimes classified as homooligosaccharides or heterooligosaccharides depending on the type and combination of constituent monosaccharides and their bond patterns, but either may be used.

These sugars may be used alone or in combination of two or more.

Furthermore, the orally dissolving compression-molded product of the present invention is primarily composed of sugars with low moldability. Specifically, the blending ratio of sugars with high moldability to sugars with low moldability is 2 to 20%, preferably 5 to 10%.

If the content is less than 2%, the tablet will not have adequate hardness and will be prone to breakage during storage, product transportation, or when removed. If the content is more than 20%, the tablet will be too hard and will not have the desired rapid disintegration and dissolution properties in the mouth. Furthermore, taking industrial scale into consideration, a content of 5-10% is preferable for ease of granulation.

More preferably, granules are used that are prepared by granulating maltose or maltitol, which are highly moldable sugars, in an amount of 5 to 7.5% by weight based on the total weight of the orally dissolving compression-molded product, in contrast to lactose and/or mannitol, which are low-moldable sugars. The active ingredient is added during the process of mixing the low-moldability saccharide with a granule formed by granulating the low-moldability saccharide with a highly moldable saccharide; during the process of mixing a granule formed by granulating the low-moldability saccharide with a highly moldable saccharide and a granule formed by granulating the active ingredient with a highly moldable saccharide; during the process of granulating the low-moldability saccharide with the active ingredient and a highly moldable saccharide; during the process of coating the low-moldability saccharide (core) with a highly moldable saccharide (first layer), coating the active ingredient (second layer), and then granulating with a highly moldable saccharide; or during the process of coating the low-moldability saccharide with the active ingredient and granulating with a highly moldable saccharide. Therefore, the optimal amount of the highly moldable saccharide to be added is 5 to 7.5% by weight of the total weight of the orally dissolving compression-molded product, e.g., the total weight of the low-moldability saccharide or the low-moldability saccharide and the active ingredient.

The particle size distribution or particle diameter of these granules is not particularly limited as long as they have adequate fluidity, and they may have a particle size distribution suitable for general tableting. For example, the particle diameter may be 1000-10 μm.

There are no particular limitations on the active ingredients that can be used in the formulations of the present invention. Preferred examples include drugs intended for people who have difficulty swallowing tablets, the elderly, and children; drugs that can be taken without water and therefore require administration while continuing daily activities; formulations for patients with water intake restrictions; and emergency medications.

Highly useful drugs include sodium bicarbonate, dried aluminum hydroxide gel, calcium carbonate, magnesium hydroxide, magnesium aluminosilicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium alumina hydroxide, aluminum hydroxide gel, co-precipitation product of aluminum hydroxide and sodium bicarbonate, dried mixed gel of aluminum hydroxide and magnesium carbonate, co-precipitation product of aluminum hydroxide, magnesium carbonate and calcium carbonate, magnesium aluminometasilicate, bismuth dimagnesium aluminosilicate, co-precipitation product of magnesium hydroxide and aluminum potassium sulfate, antacids such as boleyi, aminoacetic acid, and Scopolia extract; serotonin 5HT3 receptor antagonists such as (R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride and its salts, ondansetron, _and granisetron; Non-steroidal anti-inflammatory drugs such as indomethacin, ibuprofen, ibufenac, alclofenac, diclofenac, mefenamic acid, flurbiprofen, flufenamic acid, ketoprofen, phenylbutazone, and methyl salicylate; steroidal anti-inflammatory drugs such as cortisone, hydrocortisone, prednisolone, dexamethasone, betamethasone dipropionate, betamethasone valerate, prednisolone, triamcinolone, and fluocinoloacetonide; diuretics such as bendroflurothiazide, tetrachlorothiazide, trichlormethiazide, cyclobenzyl azide, pentylhydrochlorothiazide, hydrochlorothiazide, and bumetanide; Antipsychotics such as emonapride, diazepam, nitrazepam, flunitrazapam, lorazepam, prazepam, fludiazepam, clonazepam, chlorpromazine, reserpine, clofulberylol, trifluperidol, haloperon, promperidol, etizolam, etc.; Hypnotics such as barbital, thiopental, phenobarbital, cyclobarbital, lormetazepam, triazolam, alprazolam, etc.; Antiepileptics such as ethosuximide, sodium valproate, acetazolamide, meprobamate, etc.; Anti-Parkinson's agents such as chlorzoxazone, levodopa, etc.; Antiemetics such as metoclopramide, metoclopramide hydrochloride, etc.; Hormones such as insulin, testosterone, methyltestosterone, progesterone, estradiol, etc. analgesics such as morphine, aspirin, codeine, acetanilide, aminopyrine, loxiriprofen, etc.; sulfa drugs such as sulfamine, sulfamonomethoxine, sulfamethizole, etc.; coronary vasodilators such as nitroglycerin, isosorbide dinitrate, pentaerythritol tetranitrate, propanyl nitrate, dipyridamole, papaverine hydrochloride, etc.; _H2 receptor antagonists such as famotidine, cimetidine, ranitidine hydrochloride, loxazine acetate hydrochloride, etc.; antiarrhythmic therapeutic agents such as ajmaline, pindolol, propranolol, quinidine, amrinone, milrinone, etc.; cardiac stimulants such as caffeine, digoxin, digitoxin, etc.; calcium channel blockers such as nicardipine hydrochloride, diltiazem hydrochloride, nivadipine, nifedipine, nitrendipine, nisoldipine, nimodipine, niludipine, etc. Antihistamines such as diphenhydramine hydrochloride, carbinoxamine, diphenylpyraline, fenbenzamine, chlorpheniramine maleate, brompheniramine maleate, diphenylimidazole, and clemizole; antibiotics such as tetracycline, oxytetracyline, methacycline, doxycycline, minocycline, chloramphenicols, erythromycins, lincomycin, penicillin G, clindamycin, kanamycin, chloramphenicol, fradiomycin, streptomycin, and gentamicin; anticancer agents such as 5-fluorouracil, uracil, cytarabine, floxuridine, busulfan, actinomycin, bleomycin, and mitomycin; diabetes drugs such as glibenclamide and epalrestat; gout treatment drugs such as allopurinol, colchicine, and benzbromarone; antiallergic agents such as ketotifen fumarate, sodium cromoglycate, amlexanox, etc.; antihypertensive agents such as clonidine, atenolol, doxazosin, bilibrolol, cilazapril, lisinopril, nilvadipine, manidipine, isolyl nitrate, diltiazem, nicorandil, guanethidine sulfate, amosulalol hydrochloride, alacepril, delapril hydrochloride, enalapril maleate, etc.; central nervous system agents such as indeloxazine hydrochloride, thiaburide hydrochloride, bifemelane hydrochloride, etc.; K-channel activators such as YM934 (2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide), etc.; skeletal muscle relaxants such as dantrolene sodium, etc. antispasmodics such as eperisone hydrochloride, tizanidine hydrochloride, butylscopolamine, atropine methyl bromide, etc.; antihyperlipidemic agents such as simvastatin, bravastatin sodium, etc.; bronchodilators such as formoterol fumarate, salbutamol sulfate, procaterol hydrochloride, etc.; alpha-adrenergic receptor blockers such as tamsulosin hydrochloride, bravastatin, etc.; hypoglycemic agents; oral contraceptives; analgesics and anti-inflammatory agents such as loxoprofen; gastrointestinal motility improving agents such as dombridone, cisapride; antigastritis and antigastric ulcer agents such as deprenone; osteoporosis agents such as alfacalcidol; prostatic hyperplasia agents such as chlormadinone acetate; expectorants such as amproxol; agents for allergic rhinitis such as oxatomod, ketotifen; asthma agents such as azelastine, procaterol, terfenadine, etc.; and veterinary drugs having antipyretic, analgesic, anti-inflammatory activity, peptic antiulcer activity, etc., or veterinary drugs for each organ such as the reproductive organs.

Furthermore, since the product of the present invention is taken by disintegrating and dissolving in the oral cavity, it can also be used when an active ingredient is to be absorbed orally, if necessary. From this perspective, in addition to the above-mentioned drugs, peptides can also be used.

Representative peptides that can be effectively used as active ingredients in the present invention include various polypeptides, proteins, and their derivatives that are easily degraded in the upper gastrointestinal tract and absorbed in the lower gastrointestinal tract to exhibit physiological activity. Examples of such hormones include insulin, calcitonin, angiotensin, vasopressin, tesmopressin, LH-RH (luteinizing hormone-releasing hormone), somatostatin, glucagon, oxytocin, gastrin, cyclosporine, somatomedin, secretin, h-ANP (human atrial natriuretic peptide), ACTH (adrenocorticotropic hormone), MSH (melanocyte-stimulating hormone), β-endorphin, muramyl dipeptide, enkephalin, neurotensin, pombesin, VIP (vasoactive intestinal peptide), CCK-8 (cholecystokinin-8), PTH (parathyroid hormone), CGRP (calcitonin gene-related peptide), TRH (thyrotropin-releasing hormone), endothelin, and hGH (human growth hormone), as well as cytokines such as interleukins, interferons, colony-stimulating factors, and tumor necrosis factors, and their derivatives.

The above peptides and proteins include not only naturally occurring peptides and proteins but also pharmacologically active derivatives and analogs thereof. Thus, for example, calcitonin of interest in the present invention includes not only naturally occurring products such as salmon calcitonin, human calcitonin, porcine calcitonin, eel calcitonin, and chicken calcitonin, but also analogs such as [Asul,7]-eel calcitonin (elcatonin). Furthermore, insulin of interest includes human insulin, porcine insulin, and bovine insulin, as well as their genetically modified analogs.

Preferred drugs used in the present invention include famotidine, tamsulosin hydrochloride, and YM934.

Furthermore, the properties of the present invention can be utilized in a variety of applications, including not only pharmaceuticals but also diagnostic chemicals such as contrast agents, health foods and functional foods, oral medications such as breath fresheners and dental plaque stains, and the range of active ingredients is not particularly limited.

The amount of active ingredient to be added depends on the nature of the active ingredient, but is 50 wt% or less, preferably 20 wt% or less, of the total solid components.

The raw material for the orally dissolving compression-molded product of the present invention is a granulation of a sugar with low moldability with a sugar with high moldability. Using this raw material, it is possible to produce an orally dissolving compression-molded product with rapid disintegration and dissolution in the oral cavity. Therefore, the active ingredient can be added at any stage during the production of the compression-molded product to achieve the desired purpose. The active ingredient may be located in any part of the orally dissolving compression-molded product of the present invention.

Specifically, examples include, but are not limited to, (I) a material consisting of a granulation product obtained by granulating an active ingredient and a sugar with low moldability with a sugar with high moldability; (II) a material consisting of a granulation product obtained by granulating a sugar with low moldability with a sugar with high moldability and a medicinal ingredient; (III) a material consisting of a granulation product obtained by granulating a sugar with low moldability with a sugar with high moldability and a granulation product obtained by granulating an active ingredient with a sugar with high moldability; (IV) a material consisting of a granulation product obtained by granulating a sugar with low moldability with an active ingredient and a sugar with high moldability; (V) a material in which a sugar with low moldability (core) is coated with a sugar with high moldability (first layer), then coated with an active ingredient (second layer), and further granulated with a sugar with high moldability (third layer); and (VI) a material in which a sugar with low moldability is coated with an active ingredient and then granulated with a sugar with high moldability.

The active ingredient may be added anywhere in the composition and at any stage.

Particularly desirable forms include (V) above when the dosage of the active ingredient is extremely small and ensuring content uniformity is an issue. Furthermore, (I) or (III) above are preferred when the active ingredient has low moldability.

Therefore, the orally dissolving compression-molded product of the present invention comprises an active ingredient, a sugar with low moldability, and a sugar with high moldability, and is produced by compressing and molding a granulation product that is finally granulated with the sugar with high moldability.

Generally, it is preferred that the active ingredient used be one that does not have an unpleasant taste when dissolved. If the active ingredient does have an unpleasant taste, it is preferred that the active ingredient be treated with an appropriate taste masking agent (e.g., WO 92/09275).

Furthermore, for active ingredients for which sustained release is desired, it is preferable to subject them to an appropriate sustained-release treatment (e.g., CA2038400-0) using known methods to produce particles that control the release of the active ingredient.

The present invention provides tablets with sufficient strength for handling, particularly for pharmaceutical use, and can be used in practical applications similar to conventional tablets. Here, "sufficient strength for pharmaceutical use" refers to the minimum strength required for conventional PTP packaging. This strength is also considered sufficient for other handling, such as shipping and transport.

The strength of a tablet in the longitudinal direction is an indicator of the strength required for a PTP package, i.e., the strength required for a drug product to be extruded and removed from a typical PTP package. This hardness varies depending on the size and shape of the tablet; for example, a hardness of 1.0 kg or more is preferred for a tablet with a diameter of approximately 8.0 mm, 1.5 kg or more for a tablet with a diameter of approximately 10.0 mm, and 2.0 kg or more for a tablet with a diameter of approximately 12.0 mm. The formulations of the present invention are strong enough to withstand removal from PTP packages regardless of their size.

Furthermore, a strength suitable for bottle packaging (packaging in which tablets are sealed in a container such as glass or plastic) is preferably 3.0 kg or more, i.e., the strength of a tablet that can withstand contact between tablets or between the tablet and the container wall during transportation in a typical bottle container. The formulation of the present invention has a strength sufficient to withstand transportation or transportation in a bottle package.

"Rapid disintegration and solubility" in the present invention means that the tablet has sufficient disintegration or solubility in saliva for practical use, even without swallowing water. While this may vary from person to person, "sufficient disintegration or solubility for practical use" generally refers to disintegration or dissolution in the oral cavity within approximately 1 to 120 seconds, preferably approximately 1 to 60 seconds, and more preferably approximately 1 to 40 seconds.

The structure of the present invention is rapidly weakened by saliva in the oral cavity and gradually disintegrates or dissolves. However, it can be disintegrated or dissolved in a shorter time by pressure in the oral cavity, i.e., pressure from the upper jaw and tongue or a "licking" motion with the tongue.

For people with dry mouths or little saliva, this preparation can be applied by using water or hot water just enough to moisten the mouth.

The present invention can also be swallowed with a small amount of water after disintegrating or dissolving in the mouth, or in a partially disintegrated or dissolved state. Even in this dosage method, the benefits of the present invention, such as ease of swallowing and the small amount of water required, can be enjoyed.

Furthermore, there is no problem with taking the formulation of the present invention directly with water, just like a regular tablet. As long as there are no restrictions due to the active ingredients contained, the dosage method of the formulation of the present invention can be selected according to the patient's preference or the situation.

(Manufacturing Method) The manufacturing method for the melt-type compression-molded product of the present invention will now be described in detail, but this does not limit the scope of the present invention.

First Manufacturing Method: A medicinal ingredient is added to a sugar with low moldability and granulated with a sugar with high moldability. This granulation consists of particles of the medicinal ingredient and sugar particles with low moldability bound together by a sugar with high moldability. It is preferable to further granulate the granulation with a sugar with high moldability. The resulting granulation is then compressed to produce, for example, an orally dissolving tablet.

Second Manufacturing Method: A sugar with low moldability is granulated with a sugar with high moldability. The granules are mixed with the active ingredient, and the mixture is compressed to produce, for example, an orally dissolving tablet.

Manufacturing Method 3: A sugar with low moldability is granulated with a sugar with high moldability to obtain a granulated product. Separately, a medicinal ingredient is granulated with a sugar with high moldability to obtain a granulated product. These granulated products are then mixed, and the mixture is compressed to obtain, for example, an orally dissolving tablet.

Process 4: A sugar with low moldability is granulated with a medicinal ingredient and a sugar with high moldability. The resulting granules are compressed to produce, for example, an orally dissolving tablet.

Manufacturing Method 5: A low-moldability sugar (core) is coated with a highly moldable sugar (first layer), then coated with a medicinal ingredient (second layer), and further granulated with a highly moldable sugar (third layer). The resulting granules are compressed to produce, for example, an orally dissolving tablet.

Manufacturing Method 6: A sugar with low moldability is coated with a medicinal ingredient and then granulated with a sugar with high moldability. The resulting granules are compressed to produce, for example, an orally dissolving tablet.

The granulation method involves, for example, mixing the medicinal ingredient, sugars with low compactibility, and other additives using a fluidized bed granulator (Okawahara Manufacturing Co., Ltd.), a vertical mixer (Sanei Manufacturing Co., Ltd.), an agitation granulator (Fukae Industries Co., Ltd.), etc., and then coating and/or granulating with an aqueous solution of sugars with high compactibility as a binder. Specifically, when granulation is performed using a fluidized bed granulator, granulation is performed to the desired particle size using commonly used means, for example, a spray pressure of 0.3 to 2 kg/ ^cm2 and a product temperature of 20 to 30°C. In this case, the effects of the present invention can be further enhanced by using part of the binder to perform fine particle coating by a side spray method as a pretreatment for granulation.

Compression molding methods include tableting. Equipment commonly used for tablet molding is used, such as a single-punch tablet press (manufactured by Kikusui Seisakusho) or a rotary tablet press (manufactured by Hata Seisakusho). The tableting pressure during tableting can be set arbitrarily based on the hardness and solubility of the molded product, and is not particularly limited. The orally dissolving compression-molded product of the present invention can be further enhanced in tablet hardness while maintaining its solubility by appropriately employing a process such as spraying with a physiologically acceptable organic solvent or water and drying, or a process such as humidification and drying.

The present invention may contain various additives commonly used in tablet production, as long as the effects of the present invention are not impaired.

Examples of such additives include disintegrants, binders, acidulants, foaming agents, artificial sweeteners, flavorings, lubricants, and coloring agents.

Examples of disintegrants include starches such as corn starch and potato starch, and calcium carbonate. Examples of binders include gum arabic, gelatin, and pullulan.

Examples of acidulants include citric acid, tartaric acid, and malic acid. Examples of foaming agents include baking soda. Examples of artificial sweeteners include sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, and thomatin.

Flavoring agents include, for example, lemon, lemon-lime, orange, and menthol. Lubricants include, for example, magnesium stearate, sucrose fatty acid esters, polyethylene glycol, talc, and stearic acid. Coloring agents include, for example, food colors such as Food Yellow No. 5, Food Red No. 2, and Food Blue No. 2; food lake colors; and red iron oxide.

These additives can be added in appropriate amounts, one or more of them, during the manufacturing process of the orally dissolving compression-molded product, for example, when mixing the active ingredient with a sugar with low moldability, when mixing the active ingredient with a coating solution dissolved in water together with a sugar with high moldability, or before or after these steps.

INDUSTRIAL APPLICABILITY The orally dissolving compression-molded product of the present invention is primarily composed of low-moldability sugars. Specifically, the blend ratio of highly moldable sugars to low-moldability sugars is 2-20%, preferably 5-10%, thereby exhibiting the excellent solubility and accompanying disintegration properties inherent to low-moldability sugars. Furthermore, because it contains highly moldable sugars, it possesses physical properties such as moderate hardness that are problematic with conventional orally dissolving compression-molded products.

The orally dissolving compression-molded product of the present invention is produced using the standard manufacturing processes of granulation and tableting described above. Therefore, since it does not use the freeze-drying process used in conventional manufacturing methods for orally dissolving solid compositions, it does not require special equipment and is economical and highly industrially productive.

Furthermore, the present invention has a moderate hardness, making it easy to handle during the manufacturing and distribution processes.

Furthermore, the orally dissolving compression-molded product of the present invention can also be used when an active ingredient is to be absorbed orally, if necessary.

The hardness test is carried out by a conventional test method, for example, by subjecting the tablet to a Schleuniger tablet hardness tester (manufactured by Schleuniger).

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in more detail with reference to the following examples, but these examples are not intended to limit the scope of the invention.

Test Example To further explain the effects of the present invention, the tablets obtained in the examples were measured as follows.

(1) Hardness Test Measurements were made using a tablet hardness tester (Schleuniger). The test was performed 3 to 10 times (n = 3 to 10), and the average value is shown.

(2) Disintegration and dissolution test without water in the mouth: A compression-molded product was placed in the mouth of a healthy adult male without water (no moisture in the mouth), and the time it took for the compression-molded product to completely disintegrate and dissolve in the saliva alone was measured.

(3) Disintegration Test Measured according to the disintegration test method described in the 12th edition of the Japanese Pharmacopoeia (hereinafter referred to as the Pharmacopoeia disintegration test). The test was performed six times and the average value is shown.

The hardness and dissolution time in the oral cavity of the compression-molded product of the present invention are not significantly affected by the physicochemical properties or content of the active ingredient, and therefore the following examples include those that do not contain any active ingredient.

Example 1: 20 g of maltose (Hayashibara Shoji Co., Ltd.) was dissolved in 180 g of water. This maltose solution was used with 400 g of mannitol (Towa Kasei Kogyo Co., Ltd.) and granulated using a fluidized bed granulator (Okawahara Seisakusho Co., Ltd.). Up to 10 g of maltose was finely coated at a spray pressure of 3 kg/ ^cm² , and then granulated at a spray pressure of 0.5 kg/ ^cm² (average particle size: 184 µm). After drying, 0.5% magnesium stearate was added and the mixture was compressed into tablets (300 mg tablets, φ10 mm, 10 mm radius) using a rotary tablet press (Hata Seisakusho Co., Ltd.).

Number of hardness tests (n=3).

Example 2 The same procedure as in Example 1 was repeated, except that the maltose in Example 1 was replaced with maltitol (manufactured by Towa Chemical Industry Co., Ltd.). The average particle size of the granulated product was 158 μm.

Example 3 The same procedure as in Example 1 was repeated, except that the maltose in Example 1 was replaced with sorbitol (manufactured by Towa Chemical Industry Co., Ltd.). The average particle size of the granulated product was 146 μm.

Example 4 The same procedure as in Example 1 was carried out, except that the mannitol in Example 1 was replaced with lactose (manufactured by Domomilk Co., Ltd.). Hardness tests were conducted three times (n=3). The average particle size of the granules was 136 μm.

Example 5 The same procedure as in Example 1 was repeated, except that the maltose in Example 1 was replaced with an oligosaccharide (Nyuka Oligo LS-55P, Hayashibara Shoji Co., Ltd.). Hardness tests were conducted three times (n = 3). The average particle size of the granules was 192 μm.

Example 6: 200 g of lactose and 200 g of mannitol were mixed and then granulated in a fluidized bed granulator using 20 g of maltitol dissolved in 80 g of water. Granulation was carried out at a spray pressure of 0.5 kg/ ^cm² (average particle size: 202 µm). After drying, 0.5% magnesium stearate was added and the mixture was compressed into tablets (300 mg per tablet) using a rotary tablet press with a 10 mm diameter punch and a 10 mm radius. Hardness tests were conducted (n = 3).

Example 7: The mannitol in Example 1 was replaced with glucose (manufactured by Nippon Shokuhin Kako Co., Ltd.), and the same procedure as in Example 1 was repeated to obtain granules (average particle size: 295 μm). After drying, the granules were compressed into tablets (300 mg each) using an oil press with a 10 mm diameter, 10 mm radius punch at ^a pressure of 20 kg/cm².

Example 8 The glucose in Example 7 was replaced with xylitol (manufactured by Towa Chemical Industry Co., Ltd.), and the same procedure as in Example 7 was carried out.

Example 9 The same procedure as in Example 7 was carried out, except that the glucose in Example 7 was replaced with white sugar (manufactured by Nisshin Sugar Co., Ltd.). The average particle size of the granulated product was 355 μm.

Example 10: 2.832 kg of mannitol, 2.832 kg of lactose, 1.0 kg of famotidine, and 0.225 kg of aspartame were mixed. This mixture was finely coated with up to 1.0 kg of 15% aqueous maltose solution at a spray pressure of 4.0 kg/ ^cm² , followed by granulation. A water suspension of 77.8 g of β-cyclodextrin and 8.6 g of menthol was sprayed onto the granules in the same manner. After drying, 1% calcium stearate was added and the tablets were compressed into 150 mg tablets using a rotary tablet press with a punch having a diameter of 8 mm and a radius of 9.6 mm at a pressure of 84 kg/punch. The oral dissolution time was 15 seconds, and the hardness was 3.9 kg (n=5).

Example 11: 20 g of famotidine, 270 g of lactose, 40 g of mannitol, 8 g of aspartame, and 2 g of sodium citrate were mixed and granulated using 16 g of maltose dissolved in 144 g of water in a fluidized bed granulator (Okawahara Seisakusho Co., Ltd.). Up to 8 g of maltose, fine particle coating was performed at a spray pressure of 3 kg/ ^cm² , and then granulation was performed at a spray pressure of 0.5 kg/ ^cm² (average particle size: 198 µm). After granulation, a suspension of 0.34 g of menthol and 2.46 g of β-CD in heated water was sprayed on the mixture in the same manner. After drying, 0.5% magnesium stearate was added and the mixture was compressed into tablets (355.3 mg per tablet) using a rotary tableting machine (Hata Seisakusho Co., Ltd.) with a punch having a diameter of 10 mm and a radius of 10 mm at a pressure of 133 kg/punch. The disintegration and dissolution time in the oral cavity was 15 seconds, and the hardness (n=3) was 3.8 kg.

Example 12: 21 g of maltose was dissolved in 189 g of water. A mixture of 396.9 g of mannitol and 3.5 g of gripenclamide was granulated using this maltose solution in a fluidized bed granulator. Up to 8 g of maltose was finely coated at a spray pressure of 3 kg/ ^cm² , followed by granulation at a spray pressure of 0.6 kg/ ^cm² (average particle size 127 µm). After drying, 0.5% magnesium stearate was added and the tablets were compressed into 300 mg tablets using a rotary tablet press with a 10 mm diameter, 10 mm radius punch at a pressure of 319 kg/punch. The oral disintegration and dissolution time was 15 seconds, and the hardness (n = 10) was 3.0 kg.

Example 13: 400 g of mannitol was granulated using 10 g of maltose dissolved in 90 g of water in a fluidized bed granulator (Okawahara Seisaku Co., Ltd.) (average particle size: 98 μm). Fine particle coating was performed at a spray pressure of 3 kg/ ^cm² . After drying, the granules were compressed into tablets (300 mg each) at a pressure of 50 kg/ ^cm² using an oil press with a 10 mm diameter, 10 mm radius punch. The disintegration and dissolution time in the oral cavity was 15 seconds, and the hardness (n=3) was 4.8 kg.

Example 14: 35 g of maltose was dissolved in 140 g of water. 350 g of mannitol was granulated using this maltose solution in a fluidized bed granulator (Okawahara Manufacturing Co., Ltd.). Up to 16 g of maltose was coated with fine particles at a spray pressure of 3 kg/ ^cm² , and then granulated at a spray pressure of 0.5 kg/ ^cm² (average particle size: 329 µm). After drying, 0.5% magnesium stearate was added and the tablets were compressed into 300 mg tablets using a rotary tablet press with a 10 mm diameter, 10 mm radius punch. The oral disintegration and dissolution time was 18 seconds, and the hardness (n = 3) was 3.0 kg.

Example 15: A mixture of 4 kg of mannitol and 4 kg of lactose was granulated using a fluidized bed granulator (Okawahara Manufacturing Co., Ltd., FLO-5) with a maltose solution. Up to 0.2 kg of maltose was applied, a 10% maltose solution was used for fine particle coating at a spray pressure of 3 kg/ ^cm² . Subsequently, 0.4 kg of maltose was applied to a 30% maltose solution at a spray pressure of 1.5 kg/ ^cm² (average particle size: 140 µm). After drying, 240.4 g of this granule was mixed with 8.3 g of famotidine and 1.25 g of magnesium stearate and compressed into tablets (300 mg each) using a rotary tablet press with a 10 mm diameter, 10 mm radius punch. The oral disintegration and dissolution time was 20 seconds, and the hardness (n = 5) was 3.6 kg.

Example 16: Eight kg of mannitol was granulated using an aqueous maltose solution in a fluidized bed granulator (FLO-5, Okawara Seisakusho Co., Ltd.). Up to 0.2 kg of maltose, a 10% aqueous maltose solution was used to perform fine particle coating at a spray pressure of 2.5 kg/ ^cm2 , and then 0.4 kg of maltose was used as a 20% aqueous maltose solution to perform granulation at a spray pressure of 1.5 kg/ ^cm2 .

Separately, 500 g of acetaminophen was mixed with 25 g of maltose to form a 10% aqueous solution, and granulated using a fluidized bed granulator (Uniglat, Okawara Seisakusho Co., Ltd.).

63 g of this acetaminophen granules (average particle size: 120 μm) were mixed with 235.5 g of the previous mannitol granules (average particle size: 134 μm) and 1.5 g of magnesium stearate, and the mixture was compressed into 300 mg tablets using a rotary tablet press with a 10 mm diameter, 10 mm radius punch. The oral disintegration and dissolution time was 20 seconds, and the hardness (n=5) was 4.1 kg.

Example 17: A mixture of 487.5 g of mannitol and 162.5 g of lactose was granulated using a fluidized bed granulator (Uniglat, Okawara Seisakusho Co., Ltd.). A 10% maltose solution was used to finely coat the maltose up to 13 g at a spray pressure of 3 kg/ ^cm². Then, a solution of 138 mg of YM934 (2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide) dissolved in 50 ml of methanol was used for coating under the same conditions. Then, 19.6 g of maltose was granulated using a 20% maltose solution at a spray pressure of 1.3 kg/ ^cm² .

After drying, 628.1 g of this granules (average particle size 161 μm) was mixed with 1.89 g of magnesium stearate and compressed into tablets (294 mg per tablet) using a rotary tablet press with a 10 mm diameter, 10 mm radius punch. In a Japanese Pharmacopoeia disintegration test, the disintegration time was 25 seconds and the hardness (n=10) was 4.5 kg.

Example 18: 8 kg of mannitol was granulated using 2.67 kg of a 15% maltose aqueous solution in a fluidized bed granulator (Okawahara Manufacturing Co., Ltd., FLO-5) and dried. At this time, up to 1.0 kg of the maltose aqueous solution, fine particle coating was performed at a spray pressure of 3.0 kg/ ^cm² , and then granulation was performed. Separately, 500 g of calcium carbonate was suspended in an aqueous solution prepared by dissolving 50 g of maltose in 367 g of water. This suspension was spray-dried (Okawahara Kakoki Co., Ltd.). 110 g of the resulting spray-dried product was blended with 132 g of the previously granulated mannitol granules, 20 g of magnesium hydroxide, and 1.2 g of magnesium stearate, and the mixture was compressed into tablets (525 mg per tablet) using a rotary tablet press with a punch having a diameter of 11 mm and a radius of 11 mm, at a pressure of 154 kg/punch. The oral dissolution time was 25 seconds and the hardness was 3.7 kg (n=5).

Example 19: Salmon calcitonin (10 mg), gelatin (100 mg), and mannitol (890 mg) were mixed in a mortar to prepare a 100-fold trituration of salmon calcitonin. This was mixed with 8 g of the mannitol granules prepared in Example 18, and the mixture was compressed into tablets (112.5 mg per tablet, equivalent to 500 IU of salmon calcitonin) using an oil press with a φ8 mm, 9.6 mmR punch at a pressure of 20 kg/ ^cm² to obtain the product of the present invention. The oral dissolution time was 10 seconds, and the hardness was 5.9 kg (n=5).

───────────────────────────────────────────────────── Continued from the front page (81) Designated Countries: EP (AT, BE, CH, DE, DK, ES, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG), AP (KE, MW, SD, SZ), AM, AU, BB, BG, BR, BY, CA, CN, CZ, E E, FI, GE, HU, JP, KE, KG, KR, KZ , LK, LR, LT, LV, MD, MG, MN, MW, MX, NO, NZ, PL, RO, RU, SD, SI, S K, TJ, TT, UA, US, UZ, VN (Note) This publication is based on the publication of the internationally published Japanese patent application (Japanese utility model registration application) related to this publication. The effect of the international publication of the Japanese patent application (Japanese utility model registration application) related to this publication arises pursuant to Article 184-10, Paragraph 1 of the Patent Act (Article 48-13, Paragraph 2 of the Utility Model Act) and is unrelated to this publication.

Claims (19)

[Claims] 1. An intraoral dissolving compression-molded product containing sugars with low moldability and sugars with high moldability, which has rapid disintegration and dissolution in the oral cavity. 2. An intraoral dissolving compression-molded product that contains a granulation product obtained by granulating a sugar with low moldability with a sugar with high moldability, and that has rapid disintegration and dissolution properties in the oral cavity. 3. The compression-molded product dissolving in the oral cavity according to claims 1 or 2, which contains an active ingredient. 4. The orally dissolving compression-molded product according to claim 3, wherein the sugar having low moldability is at least one selected from the group consisting of lactose, mannitol, glucose, sucrose, and xylitol. 5. The compression-molded product dissolving in the oral cavity according to claim 3, wherein the highly moldable sugar is at least one selected from the group consisting of maltose, maltitol, sorbitol, and oligosaccharides. 6. The compression-molded product dissolving in the oral cavity according to claim 3, wherein the blending ratio of the sugars with high moldability to the sugars with low moldability is 2 to 20%. 7. The oral dissolving compression molded product according to claim 3, which is a tablet. 8. A method for producing an orally dissolving compression-molded product that disintegrates and dissolves rapidly in the oral cavity, by granulating a sugar with low moldability with a sugar with high moldability, and then compressing the granules. 9. A method for producing the orally dissolving compression-molded product according to claim 8, which contains an active ingredient. 10. The method for producing an orally dissolving compression-molded product according to claim 9, comprising granulating the active ingredient and a saccharide with low moldability with a saccharide with high moldability, and then compressing the granulated product. 11. The method for producing an orally dissolving compression-molded product according to claim 9, comprising granulating a saccharide having low moldability with a saccharide having high moldability, mixing the granulated product with the active ingredient, and then compression-molding the mixture. 12. A method for producing an orally dissolving compression-molded product according to claim 9, comprising mixing a granulation product obtained by granulating a sugar with low moldability using a sugar with high moldability and a granulation product obtained by granulating an active ingredient with a sugar with high moldability, and then compressing the mixture. 13. The method for producing an orally dissolving compression-molded product according to claim 9, comprising granulating a saccharide having low moldability with an active ingredient and a saccharide having high moldability, and then compressing the granulated product. 14. A method for producing an orally dissolving compression-molded product according to claim 13, in which a sugar having low moldability (core) is coated with a sugar having high moldability (first layer), then coated with an active ingredient (second layer), and then granulated with a sugar having high moldability (third layer), forming a three-layer structure, and then the granulated product is compression-molded. 15. The method for producing an orally dissolving compression-molded product according to claim 9, wherein the sugar having low moldability is at least one selected from the group consisting of lactose, mannitol, glucose, sucrose, and xylitol. 16. The method for producing an orally dissolving compression-molded product according to claim 9, wherein the highly moldable sugar is at least one selected from the group consisting of maltose, maltitol, sorbitol, and oligosaccharides. 17. The method for producing an orally dissolving compression-molded product according to claim 9, further comprising using at least one agent selected from the group consisting of disintegrants, binders, acidulants, foaming agents, artificial sweeteners, flavorings, lubricants, and coloring agents. 18. The method for producing an orally dissolving compression-molded product according to claim 9, wherein the compression molding is tableting. 19. A method for producing a molded product that dissolves quickly in the oral cavity, containing sugars with low moldability and sugars with high moldability.