TW200826962A - Oral solid composition masking bitterness - Google Patents

Abstract

The present invention provides an oral solid composition for masking bitterness of medicine with bitter taste. The oral solid composition is obtained by making granules from composition including (A) medicine with bitter taste and (B) hydrophilic macromolecules with the existence of water, and then drying the granules to contain water content of less than 7.5 mass percentage.

Description

200826962 IX. Description of the Invention: [Technical Field of the Invention] The present invention relates to a mouth-to-mouth composition for masking the bitterness of a bitter-tasting drug. [Prior Art] When a patient takes a bitter-tasting drug, the powder or granule must be masked for its unpleasant taste in the mouth because it cannot be taken directly. As such a method, it has been proposed to add a sweet taste such as aspartame and high sweetness.

Method of U-material (Patent Document 1); method of occlusion by occluding compound (Patent Document 2), and method of coating with gastric-soluble polymer, enteric polymer, water-insoluble polymer, wax, etc. Documents 3 and 4). It has been clarified that the drug is ibuprofen, anhydrous caffeine, chlorpheniramine maleate, diclofenac sodium (4) mountain as sodium, or allyl isopropyl acetamide (aUyl is〇pr In the case of 〇pyiacetyi urea), the composition contains more than 3% by weight of the drug and water swellable substance (low substitution degree by propyl cellulose, slow methyl cellulose, or croscarmellose) In the case of sodium, the oral preparation obtained by wet granulation in water or aqueous alcohol can not reduce the dissolution of the drug, but: the concealer: the taste of the drug which is not (four) taste (Patent Documents 5 and 6) . However, in the method of adding a high-sweetness sweetener, bitterness is sometimes not masked by the drug'. Further, the method of occlusion also has a method in which the drug is not re-released from the occluded compound, and the biological usability is lowered, and the method of 'visual bitterness and the like is strong, and ##: The coating agent is unique in the use of the crude two 125850.doc 200826962 feeling, which in turn has the following disadvantages: not only the coating agent causes the dissolution of the drug to decrease, and the 'coating (four) cost and coating step is high cost water swelling The W method does not show suitability and effectiveness for (iv) phenanthrene, anhydrous caffeine, sodium, diclofenac sodium, or drugs other than propyl isopropyl acetonitrile.

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[Patent Document No. 2] Japanese Patent Laid-Open Publication No. Hei No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. Japanese Laid-Open Patent Publication No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. SUMMARY OF THE INVENTION An object of the present invention is to provide a mouth-to-mouth preparation which can prevent the bitterness of a bitter-taste drug and which can be inexpensively produced by a simple production method without the above problems. [Technical means for solving the problem] The present inventors conducted various studies on a method for preventing the bitterness of a drug, and as a result, found that a composition containing a bitter taste drug and a hydrophilic polymer is present in the presence of water. The solid composition obtained by granulation and then drying to a moisture content of 7.5 % by weight or less does not exhibit the bitterness of the drug, thereby completing the present invention. That is, the present invention relates to an oral solid preparation which comprises granulating a composition comprising a (苦) bitter taste drug and a (Β) hydrophilic polymer in the presence of water at 125850.doc 200826962, and then It is obtained by drying until the amount of water is 7.5 mass% or less. Further, the present invention relates to an oral solid preparation which is formed by mixing water (aqueous) hydrophilic high-concentration + by adding water to a hydrophilic polymer, and mixing it with a drug having a bitter taste for granulation. Then, it is dried until the amount of water becomes 7.5% by mass or less. [Effect of the Invention] The oral solid composition of the present invention can prevent the bitterness of the drug at the time of administration. [Embodiment] The following is a brief description of this book. In the present invention, the term "bitter taste" refers to a drug which has a bitter taste on the tongue when taken. Specific examples include: crude drug extracts (peony, licorice, cinnamon, jujube, ginger, and wear). Extracts of heart grass, passion fruit, hook vine, hops, human cockroaches, etc.; Chinese herbal extracts (Gegen soup, Jiefeng Jiedu soup, squeaking smashing pills, Xiaochaihu soup, Xiaoqinglong soup, Suanzaoren soup, Extracts of Shiwei Baidu Decoction); Biological Extracts (Yongtong, catechu, bear grape, wild rose, Corydalis, cypress, berberine, Polygonum, Campanulaceae, Yeast, Ginkgo biloba, Aloe, Bacteria, Turmeric, Wu Extracts of medicines, pleadings, dried ginger, etc.; vitamin B1, group (thiamine, thiamine nitrate, Bisbentiamine, octotiamine, phenyl thiamine (benf〇) Tiarnine), benzophenone thiamine, thiamine disulfide, diisobutyl thiamine, Dicethiamine Hydrochloride, vitamin & riboflavin adenosine dinucleotide, riboflavin, Ribophosphorus phosphate, riboflavin, etc.匕 group (pyridoxine, pyridoxol, mouth ratio σ polyamine 125850.doc 0 200826962 (pyridoxamine) and these hydrochloric acid or phosphate), vitamin Bi2 group (methylcobalamin) Ming, cyanomethylcobalamin, methyl mecobalamin, adenine nucleoside medramine, hydroxymethylcobalaminamine (glycine, alanine, valine, leucine, iso Amino acid, serine, threonine, phenylalanine, tyrosine, tryptophan, cystine, methionine, valine, hydroxyproline, aspartic acid, aspartic acid , face lysine, branamine, arginine, histidine, lysine, aminobutyric acid, pyrrolidonecarboxylic acid, ε-aminocaproic acid, hydrolyzed elastin (elastin), hydrolyzed collagen, Water-soluble knee protein, complex protein, glutathione, wheat peptide, soybean peptide); / Xiaohuadao medication (lebenine hydrochloride, cilostatin, pirenzepine hydrochloride); Histamine (diphenhydramine, promethazine hydrochloride); antipyretic and analgesic (aspirin, acetaminophen Ethenzamide, isopropylantipyrine; antitussive and expectorant (ephedrine hydrochloride, methylmethionine hydrochloride, codeine phosphate, codeine dihydrogen phosphate, hydrogen Dextromethorphan hydrobromide, tea test, guaifenesin, etc. In the present invention, the content of the bitter taste drug is compared with the total bitter taste drug and the aqueous hydrophilic polymer. The total mass of the material is preferably 丨~99 mass ° / 〇, more preferably 2 to 95% by mass 〇 / 0. In the present invention, first, a composition comprising (A) a bitter-taste drug and (B) a hydrophilic polymer is granulated in the presence of water, or water is added to (B) a hydrophilic polymer to form an aqueous solution. The hydrophilic polymer is mixed with (A) a bitter-taste drug for granulation; preferably, the latter method is 125850.doc 200826962.

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V The hydrophilic polymer used in the present invention contains a hydrophilic group in the molecule, and can maintain water of a mass equal to or greater than the mass of the hydrophilic polymer, and is in a state of being solid or semi-solid while maintaining water, but not Dissolved in water and thus insoluble, the hydrophilic polymer itself must not exhibit an unpleasant taste. Examples of such a hydrophilic polymer include low-substituted propylcellulose, crystalline cellulose, cross-linked slow methylcellulose sodium, crosslinked polyethylene, and retinoic cellulose.竣Methylcellulose, 竣methylcellulose, etc.; one or two or more of them may be used in combination. Among these, as the preferred hydrophilic polymer, propylene cellulose, methyl cellulose, sodium methyl ketone, and crosslinked methyl cellulose can be mentioned from a low degree of substitution. Choose from crystalline cellulose! Kind or more than two. Further, as for the particularly preferable hydrophilic polymer, propyl cellulose is used in a low degree of substitution, and it is preferred to use 5% by mass or more, particularly preferably 65% by mass or more, based on the total amount of the hydrophilic polymer. . When a propylcellulose is used as a hydrophilic polymer with a low degree of substitution, it is easy to process into a mouth-solid composition having an excellent shape and a particle diameter, and the propyloxy group is used. The content is preferably 5/1 to 16.0% by mass, more preferably 70 to 13% by weight, particularly preferably % by mass. As such a low-substituted propyl cellulose, LH-31 (hydroxypropoxy group is 10 0 to 12 9 mass%) manufactured by Shin-Etsu Chemical Co., Ltd., and LH_32 (via propyloxy group 7) .〇~99f amount%). Further, the average particle diameter of the propylene cellulose having a low degree of substitution is preferably about 6 μm or less, more preferably 45 μm or less, still more preferably 25 or less. 125850.doc -10- 200826962 The content of the hydrophilic polymer substance depends on the type of the bitter-taste drug, but the amount of the drug of the bitter taste is usually 'the hydrophilic composition of the oral solid composition containing the above-mentioned Bilizhi. More than or equal to the mass of the substance. .3 parts by weight or more. In the present invention, the term "aqueous hydrophilic polymer material" means a substance having a solid or semi-solid shape in a water-preserving temple. Ratio of water to hydrophilic polymer in water-containing hydrophilic polymer f

The type of water-based rain molecule 1 贞 or the type or amount of bitter-tasting drug is timely and Λ. The preferred 疋 is roughly water: hydrophilic polymer = 1 to 1 〇: range of 1, more preferably 2 to 5: 1. In the aqueous hydrophilic polymer material, the water retained in the hydrophilic polymer may be water alone or may be added with a small amount of alcohol. In the case of adding alcohol: the content of the alcohol, in terms of the mass ratio, is preferably the total amount of water retained: 5::: 〇 mass% or less, more preferably 25% by mass or less, most preferably 1 5 罝%% below 0 again, 5 As for knowing, Tong 10 uses ethanol. The temperature of the water held in the hydrophilic south is preferably in the range of eight machines and in the range of 5 to 30 °C. In the π-solid composition of the present invention, in addition to the bitter-tasting drug and the aqueous hydrophilic polymer material, the other pharmaceutically active ingredient may be appropriately formulated according to the purpose or generally used for medicine or food. The success! For example, as for the pharmacologically active ingredients, there may be mentioned: antipyretic town, inflammatory, hypnotic, calming, sleepiness inhibitor, anti-corona, pediatric analgesic, health: medicinal, antacid, digestive, cardiotonic, arrhythmia t, Blood pressure lowering, vasodilator, diuretic, anti-ulcer drug, colon drug, osteoporosis 125850.doc 11 - 200826962 Therapeutic medicine, antitussive and expectorant, nourishing strong agent, only raw boast, ..., antibacterial agent, frequent urination Improvement, as well as the pharmacologically active ingredients that can be used in medicine. (Thin _, bonding: smashing: Γ: the component' can be exemplified by excipients, agents, etc. For example, as for the flavors/flavors, flavors, sugar, trehalose, etc., mention: lactose, refined Sugar alcohol such as white sugar, glucosinolate, etc. As for the binder erythrol propyl methyl ketone, y y y y y y y y y y y y y y y y y y y y y y y y y Starbucks such as Guru, wheat house powder, etc. As for sweeteners, licorice can be harvested, stevia extract is used as a flavoring/fragrance, 1, and polysaccharides are selected. For the coloring agent, titanium dioxide, U "dye, dyes suitable for food and pharmaceutical use, etc.. Water-to-mouth solid composition can be used by itself. The bitter-taste drug is prepared by removing water from the mixture of the two-parent and the sub-substance. The measurement of the two amounts is, for example, 5 Torr. Until the water is 7 or less, especially preferably 2% or less. As for removing moisture The method is as follows: a method of removing moisture by using a box dryer or a fluidized layer granulation dryer, and drying by heat drying or drying under reduced pressure. "Uneven mixture of the drug and the aqueous hydrophilic polymer substance , 125850.doc -12- 200826962 can be prepared by adding water to a hydrophilic polymer to prepare a hydrophilic hydrophilic polymer substance, and then adding a bitter taste drug and then uniformly mixing; and: also, a bitter taste drug and After the hydrophilic polymer is mixed, the water is slowly added, and then mixed and prepared in a uniform manner. Among them, it is preferred that the front-side. & ° is a simple mixture of a bitter taste drug and a hydrophilic polymer. Combination _16, or the dry granulation of a bitter-tasting drug and a hydrophilic polymer, the effect of sufficiently masking bitterness cannot be obtained. Further, the mixture of the bitter-taste drug and the aqueous hydrophilic polymer substance is mixed. '4' can be prepared by wet granulation, which is usually used in the fields of medicine or food, such as agitation granulation, flow layer granulation, extrusion granulation, etc. When the granulation method is combined, the preparation can be carried out simply, for example, by adding a bitter taste drug and a hydrophilic polymer, and then adding other additives as needed, and stirring the mixer such as a vertical granulator. After mixing with a mixer such as (venicai granulat〇r) (manufactured by p〇wrex), the purified water is slowly added in an amount of from i to 10 times the hydrophilicity of the molecule (J, /亍) A uniform mixture of the toxic drug and the aqueous hydrophilic polymer material. The granulator is extruded by an extrusion granulator, such as Fine Granulat (i), which is granulated, and the mixture is granulated. The particulate composition' thus produces a homogeneous mixture of bitter taste and aqueous hydrophilic 7 knife material. Further, the mixture may be made into a granule of a target particle size by a sieve, and then subjected to a spherical treatment by a spherical granulator (4), which is made of a granule, to prepare a wet granule composition. _ Remove water from a homogeneous mixture of the above-mentioned bitter-tasting drug and aqueous hydrophilic polymer material. Finally, use a sieve to make it into a target particle size of 125850.doc -13- 200826962. In the present invention, the particle size of the granules may be any one of the granules of the powder or the granules and the granules, and the sensation of the sensation or the drug may be taken into consideration, and the saccharide or the polymer may be obtained. Dry granule coating. In the present invention, when the particle diameter is measured by the sieving method, the average particle diameter of the particles obtained by dryness is preferably 25 or more, more preferably 50 to 1500 μm, and particularly preferably 100 to 1. 〇〇〇μιη. In the present invention, the particle diameter of the particles can be easily adjusted by changing the sieve diameter of the extrusion granulator.

The orally-sealed composition thus produced has a granular shape and suppresses bitterness of a bitter-taste drug, and further has good fluidity. Therefore, the granules of the oral solid composition can be directly used as a powder, a fine granule, and a granule. Alternatively, it may be filled into a hard capsule or a soft capsule to be used as a capsule, or the pellet of the solid composition may be tableted into a tablet. Further, these capsules or tablets may be coated with a saccharide or a polymer. In the preparation of these preparations, the sputum additives which are usually used in medicines or foods, such as stabilizers, stabilizers, interfacial enthalpy, plastics, squeezing agents, lubricants, reducing agents , sweeteners, diluents, adsorbents, bridge odorants, chelating agents, antioxidants, glossing agents, coating agents, perfumes, coatings, fillers, defoamers, cooling agents "and chews, Coloring agent, scenting agent, sugar coating agent, foaming agent, excipient, disintegrating agent, disintegrating agent dissolving agent, fragrance, anti-wetting agent, preservative, preservative, antistatic agent, increment Agents, seasonings, sour materials, sweeteners: coloring materials, seasonings, fortifiers, bulking agents, preservatives, anti-mold agents, anti-emulsifiers/bleaches, viscosity-enhancing stabilizers, bitter substances , 125850.doc -14- 200826962 Luster, manufacturing agent, etc. Further, the orally-sealed composition of the present invention thus produced and the preparation containing the same can prevent the bitterness of the drug and are therefore easy for the user to take. [Examples] Next, the present invention will be specifically described by way of examples and comparative examples, but the present invention is not limited thereto. Example 1 ~ 100 g of licorice extract powder (manufactured by Nippon Powder Pharmaceutical Co., Ltd.) (700 g of the original drug) and 3118 g of the hydrophilic polymer substance (low-substituted propylcellulose) ((hydroxypropyloxy 1 〇〇~12·9 mass%) LHpc : LH-31 : Shin-Etsu Chemical Co., Ltd.) 800 g and purified water 2318 g] mixture with vertical granulator VG-10 (Powrex (Unit)) After uniformly mixing, extrusion granulation was carried out by a wet extrusion granulator (Twin Dome Gran) TDG-80 (manufactured by Fuji Paudal Co., Ltd.) using a 整8 mm sieve, using a spherical granulator (Fuji) Paudai (share) system) Performs spherical processing. Then, it is dried by a flow drying apparatus fl〇_5a/2 〇 (made by FreUnd Industries Co., Ltd.) to produce granules having an average particle diameter of about 65.65 mm, and a four-sided aluminum heat sealing machine to make each package Subcontracting is carried out in a manner that the quality reaches 3 〇〇 mg. The granules were at 5 Torr. The dry reduction under 条件, 1 minute is 1.2%. Comparative Example 1 1 g of licorice extract powder (manufactured by Nippon Powder Pharmaceutical Co., Ltd.) and 8 g of low-substituted hydroxypropylcellulose (LHPC: LH-31: manufactured by Shin-Etsu Chemical Co., Ltd.) were uniformly mixed to The four-sided aluminum heat sealing machine is sub-packaged in such a way that the quality of each package reaches 3〇〇. 125850.doc •15- 200826962 Example 2 357.1 g (manufactured by 曰本粉药), 357.1 g (converted to 3,571 kg of crude drug), and hydrophilic hydrophilic polymer substance 1755 g (low substitution of 200 g of propylcellulose (LHpc: LHa: manufactured by Kyowa Chemical Co., Ltd.), a mixture of 300 mg of slow methyl fiber (4) (manufactured by Wude Pharmaceutical Co., Ltd.) and 1255 of purified water (§) After the vertical granulation (Powrex (|^)) was uniformly combined, the granulation was carried out by a 0.6 _ sieve of a wet extrusion granulator, which is called (4) PaudaK. Then, it was dried by a fluidized bed drying device FL〇-5A/2 (made by Freund Industries Co., Ltd.) to produce granules having an average particle diameter of about G.5 mm, which was sealed by a four-sided heat sealing machine. Subcontracting is achieved in the form of 2g. The granules had a drying loss of 丨.50/0 under machine and overnight conditions. Comparative Example 2 5 g of dried extract of Kudzu Soup (manufactured by Nippon Powder Pharmaceutical Co., Ltd.), low-substituted hydroxypropylcellulose (manufactured by LHPC ··LH-31 · Shin-Etsu Chemical Co., Ltd.) 28 g, And 42 g of carboxymethylcellulose calcium (made by Wude Pharmaceutical Co., Ltd.) were uniformly mixed, and subcontracted by a four-sided aluminum heat sealing machine in a manner of 2 § per package. Example 3 25 g of dried extract of bear grape (made by Matsuura Pharmaceutical Co., Ltd.) (converted to 2 kg of crude drug) and 1235 g of hydrophilic hydrophilic polymer substance [low-substituted hydroxypropyl cellulose] LHPC · · LH-32 · Shin-Etsu Chemical Co., Ltd. (hydroxyloxy group 7.0~9.9% by mass) 280 g, carboxymethylcellulose calcium (made by Wude Pharmaceutical Co., Ltd.) 7〇g and purified water The mixture of 885 g] was uniformly mixed with a vertical granulator VG-10 125850.doc -16 - 200826962 (Powrex), and then wet-extruded granulator Ding DG_8〇 (manufactured by Fuji Paudal Co., Ltd.) The 0.6 mm sieve was subjected to extrusion granulation. Then, it was dried by a fluidized bed drying device FLO-5A/2 (made by Freund Industries Co., Ltd.) to produce granules having an average particle diameter of about 0.5 mm, and a four-sided aluminum heat sealing machine was used to achieve a mass of 1 g per pack. The way to subcontract. The granules had a drying loss of 0.9% at 5 cc, 1 Torr. Comparative Example 3 5 g of bear raisin extract (Songpu Pharmaceutical Co., Ltd.), low substitution degree propylcellulose (LHPC: LH-32: manufactured by Shin-Etsu Chemical Co., Ltd.) 56 g, and carboxymethyl group Cellulose (five medicines) 14 g was uniformly mixed and subcontracted in a manner of 2 g per pack by means of a four-sided heat sealing machine. Example 4 1 〇〇g of bisphenyl sulfonamide (Tanabe Pharmaceutical Co., Ltd.), 1 〇〇g of Sigma sterol hydrochloride (manufactured by Daiichi Fine Chemical Co., Ltd.), and riboflavin (MitSubishi Pharma) )) 12 g, cyanoguanamine (made by DSM Nutriti〇n Japan Co., Ltd.) 1.5 g, vitamin E succinate calcium (made by Eisai Co., Ltd.) 1〇3 58 g, nicotine 醯Amine (made by DSM Nutrition Japan Co., Ltd.) 6〇g, and water-containing hydrophilic polymer substance 2032.92 g (low-substituted hydroxypropylcellulose (LHpc: LH_ 31: manufactured by Shin-Etsu Chemical Co., Ltd.) 522.92 g and purified water Mixture of 151〇g), uniformly mixed with vertical granulator VG-10 (Powrex), and then wet-type extrusion granulator TDG-80 (manufactured by Fuji Paudal Co., Ltd.) 5 mm The sieve is subjected to extrusion granulation. Then, it was dried by a fluidized bed drying device FLO-5A/2 (manufactured by Freimd Industries Co., Ltd.) to produce granules having an average particle diameter of about 0.4 mm, which was obtained by a four-sided aluminum heat sealing machine at a mass per pack. The method of 300 mg is divided into 125850.doc -17- 200826962 package. The granules had a drying loss of 0.6% at 50 ° C for 10 minutes. Comparative Example 4 bisbenzoquinone thiamine (manufactured by Tanabe Pharmaceutical Co., Ltd.) 1 〇 g, pyridoxine hydrochloride (manufactured by Daiichi Fine Chemical Co., Ltd.) 1 〇 g, riboflavin (Mitsubishi)

Pharma Corporation (manufactured by Pharma Corporation) g, cyanocobalamamine (manufactured by dSM Nutrition Japan Co., Ltd.) 〇·ΐ 5 g, vitamin E succinate calcium (manufactured by Eisai Co., Ltd.) 10.358 g, nicotinic amide ( DSm Nutrition Japan Co., Ltd.) 6 g, and low-substituted hydroxypropyl cellulose (LHPC: LH-3 1 : Shin-Etsu Chemical Co., Ltd.) 52.292 g uniformly mixed with a four-sided heat sealing machine for each package Subcontracting is carried out in a quality of 300 mg. Example 5 6 g of L_proline (manufactured by Ajinomoto Co., Ltd.), L-leucine (manufactured by Kyowa Co., Ltd.), 9 g, and L-isoleucine (Concord)酵 、 、 、 、 酵 酵 酵 酵 酵 酵 酵 酵 酵 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 (Coordination Fermentation Co., Ltd.) i2〇g, and water-containing hydrophilic polymer substance 1705 S (low-substituted hydroxypropyl cellulose (LHPC: LH-31: manufactured by Shin-Etsu Chemical Co., Ltd.) 430 § and purified water A mixture of 1275 g), which is self-mixed in a vertical < i-granulator VG-l (PoWrex), followed by a wet extrusion granulator • TDG_80 (manufactured by Fuji Paudal) The 8 mm sieve was subjected to extrusion granulation, and a spherical granulator (manufactured by Fuji Paudal Co., Ltd.) was subjected to a spherical treatment, and then, a moving layer drying device FL〇_5A/2 (manufactured by Freund Industries Co., Ltd.) was used. Drying, the granules with an average granule k of about 〇·6 mm are sub-packaged in a four-sided aluminum heat sealing machine with a capacity of 1 g per bag. The granules are at 5 〇, 125850 .doc -18- 200826962 10 minutes of conditions The amount of dry reduction was 0.9%. Comparative Example 5 6 g of L-leucine (manufactured by Ajinomoto Co., Ltd.), L-leucine (manufactured by Kyowa Co., Ltd.), 9 g, L-isoleucine ( 6g, L_ branamide (manufactured by Ajinomoto) 12 g, L-arginine (made from Ajinomoto) 12 g, L-isoamine hydrochloride Acid (Xiehe Yeast Co., Ltd.) 12 g, and low-substituted hydroxypropyl cellulose (LHPC: LH-31: Shin-Etsu Chemical Co., Ltd.) 43 g uniformly mixed with a four-sided aluminum heat sealing machine, each The package was sub-packaged in a mass of 1 g. Example 6 will contain 10 g of l-peramide (made by ISFI) and 5000 g of hydrophilic hydrophilic polymer (low-substituted hydroxypropyl fiber). a mixture of 990 g (LHpc: LH-32, manufactured by Toyo Chemical Co., Ltd.) and purified water (40 〇g), uniformly mixed with a vertical granulator VG-10 (P〇wrex) Extrusion granulation was carried out using a 0.2 mm sieve of a wet-type granulator TDG_8(R) (manufactured by Fuji Paudal Co., Ltd.), followed by a fluidized bed drying apparatus FL〇-5A/2 (made by Freund Industries Co., Ltd.). Dry, the average particle size is about 〇. 1 5 mmt Qi Qi, sub-packaged in a four-sided aluminum heat sealing machine with a mass of 5 〇〇g per pack. The granules have a drying loss of 0.5% at 5 ° C for 10 minutes. Example 6 1 g of Lebbin hydrochloride (made by ISFI) and 99 g of low-substituted hydroxypropylcellulose (LHPC: LH-32: manufactured by Shin-Etsu Chemical Co., Ltd.) were uniformly mixed with a four-sided aluminum heat sealing machine. The quality of the bag is 5 〇〇mg. Example 7 1 125850.doc -19- 200826962 Will contain diphenhydramine hydrochloride (manufactured by King Kong Chemical Co., Ltd.) 50 g, and aqueous hydrophilic polymer material 3955 g (low-substituted hydroxypropyl cellulose (LHPC: LH-;31: Shin-Etsu Chemical Co., Ltd.) 95〇g and purified water 3〇〇5 g) mixture, with vertical granulator VG-10 (Powi:ex (after uniform mixing, wet extrusion) Extrusion granulation was carried out by a 0.6 mm sieve of a granulator TDG-80 (manufactured by Fuji Paudal Co., Ltd.), and then dried by a fluidized bed drying device FL〇-5A/2 (manufactured by Freund Industries Co., Ltd.) The granules with an average grain control of about 〇·5 mm are sub-packaged in a four-sided heat sealing machine with a mass of 1 g per pack. The granules are dried at 50 ° C for 10 minutes. 0.8%. Comparative Example 7 5 g of diphenhydramine hydrochloride (manufactured by King Kong Chemical Co., Ltd.) and 95 g of low-substituted hydroxypropylcellulose (LHPC: LH-31: manufactured by Shin-Etsu Chemical Co., Ltd.) were uniformly mixed. It is sub-packaged in a four-sided aluminum heat sealing machine with a mass of 1 g per package. Example 8 will contain acetaminophen (Shanmoto Chemical Industry ( )) 225 g, ethoxybenzamide (made by SHIZUOKA COFFEIN Industrial Co., Ltd.) 285 g, water-containing hydrophilic polymer substance 1470 g (low-substituted hydroxypropyl cellulose (LHPC: 1^-31: Shin-Etsu Chemical Co., Ltd.) 390 g, 864 g of purified water, and a mixture of ethanol (Wako Chemical) 216 g) of the Pharmacy's vertical granulator VG-10 (Powrex) After uniformly mixing, extrusion granulation was carried out by a wet extrusion granulator TDG-80 (manufactured by Fuji Paudal Co., Ltd.) in a 6 mm sieve. Then, a fluidized bed drying device FLO-5A/2 (Freund) was used. The industrial (stock) system is dried to produce granules with an average particle size of about 〇·5 mm, and is sealed with a four-sided aluminum heat seal 125850.doc -20- 200826962, in a mass of 1 · 2 g per pack. The granules were dried at 50 ° C for 10 minutes, and the amount of drying was 〇, 4 〇 / 0. Comparative Example 8 acetaminophen (manufactured by Yamamoto Chemical Co., Ltd.) 22 5 g, Ethoxybenzoimide (made by SHIZUOKA COFFEIN Industrial Co., Ltd.) 285 g, and low-substituted hydroxypropyl cellulose (LHPC: LH-31: manufactured by Shin-Etsu Chemical Co., Ltd.) 39 g The mixture was sub-packaged in a four-sided aluminum heat sealing machine at a mass of 1.2 g per package. Example 9 dextromethorphan hydrobromide (manufactured by Watanabe Chemical Co., Ltd.) 40 g, theophylline ( White Bird Pharmaceutical Co., Ltd.) 200 g, chlorinated lysozyme (Eisai) 4〇g, aqueous hydrophilic polymer material 2790 g (low-substituted hydroxypropyl cellulose (LHPC: LH-31: Shin-Etsu Chemical ( A mixture of 720 g and purified water (2070 g) was uniformly mixed with a vertical granulator VG-10 (Powrex) to a wet extrusion granulator TDG-80 (Fuji Paudal) ))) 4 mm sieve for extrusion granulation. Then, it is dried by a fluidized bed drying device FLO-SAQi^eimd industry (manufactured by the company) to produce granules having an average particle diameter of about 〇·3 mm, and a four-sided aluminum heat sealing machine, which has a mass of 5 每 per pack. Subcontracting in the form of 〇mg. The granules had a drying loss of 0.9% at 50 ° C for 10 minutes. Comparative Example 9 dextromethorphan hydrobromide (manufactured by Watanabe Chemical Co., Ltd.) 4 = alkali (White Bird Pharmaceutical Co., Ltd.) 20 g, chlorinated lysozyme (Eisai) 4 g, and low degree of substitution Hydroxypropyl cellulose (LHPC: LH-31: manufactured by Shin-Etsu Chemical Co., Ltd.) 72 125850.doc -21- 200826962 The mixture is divided into four parts, and the sub-package is carried out in the form of each package. Test Example 1: A sensory test was carried out on 10 subjects, and the results are shown below. Taking, ^ : 3⁄4: For each of the preparations of Example 9 and Comparative Example U, respectively, were contained after • ^10 #钟', and the feeling of taking was compared. The evaluation was divided into grades 'for bitterness (bitterness is very strong: 5 points, bitterness is slightly stronger: 4 points, (x: no 3 knives, slightly bitterness: 2 points, no bitterness: 1 point). The results are shown in Table 1. [Table 1]

As is apparent from the above table, the bitterness of any of the preparations of the present invention is remarkably suppressed as compared with the comparative preparation, and the feeling of ingestion is excellent. [Industrial Applicability] The oral solid composition of the bitterness-taste drug of the present invention and the substance which removes moisture from the aqueous hydrophilic polymer substance can prevent the bitterness of the drug at the time of administration. The oral solid composition has a granular shape and has a good flow of 125850.doc -22-200826962. Therefore, not only the particles of the composition of the two solids can be directly formed into a powder or a fine granule. Granules and the like can also be easily added into capsules or a key, and can be widely used in pharmaceuticals, foods, and the like. Further, the orally-administered composition of the present invention can mask bitterness and can release the drug immediately after a short delay after administration. Thus, it is suitable for various immediate release preparations. Therefore, since the oral solid composition of the present invention is easy to take, it is a preparation which can be taken for a long time by many patients and which can surely exert the effects of various drugs.

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Claims (1)

200826962 X. Patent application scope: 1. The drug of the ruler of the seven-day-day Tianwei and the composition of the hydrophilic polymer of (Β) 3 are granulated in the presence of water, and then dried until the water content becomes 7.5 mass% or less. obtain. 2. An oral solid preparation which is prepared by adding water to a hydrophilic polymer (10) to prepare an aqueous hydrophilic polymer, which is mixed with (4) a bitter-taste drug, granulated, and then dried to a moisture content. Obtained under 75% by mass. Ο 3. The oral solid preparation of the present invention, which comprises 0.05 parts by mass or more of (B) a hydrophilic polymer with respect to 1 part by mass of the bitter taste drug. 4. The oral solid preparation according to claim 1 or 2, wherein the amount of water in the granulation is 丨~(7) parts by mass relative to 1 part by mass of the (B) hydrophilic polymer. 5. A composition according to claim 1 or 2 which is a granule, a fine granule, a capsule or a lozenge. 6. The composition according to claim 1 or 2, wherein (B) the hydrophilic polymer is a low degree of substitution hydroxypropylcellulose. 7. The composition of claim 1 or 2, wherein the particles obtained by drying have an average particle size of 25 μm or more. 125850.doc 200826962 VII. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 8. If there is a chemical formula in this case, please reveal the best indication of the characteristics of the invention. Chemical formula: (none) Γ 125850.doc