JP4945917B2 - Core particles for drug-containing coatings - Google Patents

Description

  The present invention relates to a particle containing a drug having an unpleasant taste at a high concentration, and relates to a drug-containing particle suitable for a coating core particle because the particle size is small and the strength is high.

  Although it is often said that it is “suffering from a good drug mouth”, the taking ability has never been good, and various masking techniques have been developed. In the field of solid preparations for internal use, techniques such as sugar coating and film coating for tablets have first spread, but in recent years, techniques for coating particles and granules themselves such as powders and granules have also been rapidly developed (see Non-Patent Document 1). .

  The need for masking is great if it is a powder or granule containing a large amount of a drug having an unpleasant taste such as a bitter taste, and the following masking techniques have been developed so far.

  First, spray the binding solution while spraying a powder containing a drug with an unpleasant taste on the surface of core particles such as sugar and crystalline cellulose having a uniform particle size distribution, or dissolve or suspend the drug. There is a layering granulation method in which the liquid is sprayed onto the core particles and then the coating liquid is sprayed thereon to mask (see Non-Patent Document 2). Since this method is originally a technique used in the manufacture of sustained-release preparations, it can be almost completely masked if it has an unpleasant taste such as a bitter taste. However, the production volume per batch is small due to the capacity of the tumbling granulator used for this, and the production takes a long time, so the production cost is very high, and the drug is contained in the core particle part. Therefore, the particles have a disadvantage that the size of the particles increases accordingly.

  Also disclosed is a method of masking by spraying a coating liquid onto granules prepared by extrusion granulation using a fluid type coating apparatus (see Non-Patent Document 3). However, a large amount of excipient is required to prepare the powder for extrusion granulation, and the stability between the drug and the excipient must be taken into account. There was a demerit.

  Therefore, in order to solve these problems, there is a demand for a method for producing coating core particles containing fewer drugs and containing the drug itself.

  Here, physical properties required for the core particle for film coating include an appropriate average particle size, a sharp particle size distribution, a high particle strength, and a heavy property. A rolling (stirring) fluidized bed granulation method is mentioned as a method for preparing particles having these physical properties. The rolling (stirring) fluidized bed granulation method is a composite granulation method having both a fluid motion by fluidized air and a rolling compaction motion by stirring as the driving force of the powder (see Non-Patent Document 4). ). This motion mechanism makes it possible to prepare granulated particles having both the sharp particle size distribution characteristic of fluidized bed granulation and the heavy characteristic characteristic of stirring granulation. Further, high particle strength, which is considered suitable for coating core particles, may be possible depending on the choice of excipient.

Japan Powder Technology Association "Fluidized Bed Handbook" Baifukan, p224-225, 1999 “Granulation Hanbook” edited by Japan Powder Technology Association, Ohm, p420-421, 1991 Japan Powder Technology Association "Fluidized Bed Handbook" Baifukan, p225-228, 1999 Japan Powder Technology Association "Fluidized Bed Handbook" Baifukan, p223-224, 1999

  An object of the present invention is to provide a core particle for coating containing a drug having an unpleasant taste such as a bitter taste at a high concentration and having a size suitable for coating, a high particle strength, and the like.

  The present inventors selected ibuprofen as a drug whose masking treatment is indispensable because it has a large amount of compounding (dose) per day and has a bitter taste, and intensively studied a method for producing coating core particles containing this ibuprofen. . As a result, the powder blended with ibuprofen, silicon dioxide (light anhydrous silicic acid), hygroscopic polymer (crystalline cellulose) and saccharide-based excipient (candy powder) was tumbled (stirred) in a fluid bed granulator. When particles are prepared by spraying a binding solution in which a binder (hydroxypropylcellulose) is dissolved in water, the particles having a particle size, particle size distribution, specific gravity, and friability suitable for coating can be prepared. I found it.

  The aspect of the present invention completed on the basis of such knowledge is that 35% by mass or more of a drug having an unpleasant taste, 1 to 10% by mass of silicon dioxide, 5 to 30% by mass of a hygroscopic polymer, and saccharides in the particles 10 to 50% by mass of a system excipient and 5 to 20% by mass of a binder, an average particle size of 100 to 400 μm, a geometric standard deviation of particle size distribution of 2.0 or less, and a friability of 7% or less It is the particle | grains characterized by being.

  In another embodiment of the present invention, 35% by mass or more of a drug having an unpleasant taste, 1 to 10% by mass of silicon dioxide, 5 to 30% by mass of a hygroscopic polymer, and 10 to 50 of a saccharide-based excipient. The powder obtained by mixing the powder containing 0% by mass to 0% by mass and the binder, fluidizing the obtained powder in a rolling (stirring) fluidized bed granulator, and spraying the binding liquid. Particles.

  Another embodiment of the present invention is the above particle, wherein the drug having an unpleasant taste is ibuprofen.

  Another aspect of the present invention is the above particles, wherein the saccharide-based excipient is at least one of candy powder, powdered sugar, erythritol, xylitol, sorbitol, maltitol, lactitol, sucrose, anhydrous maltose and hydrous maltose.

  Another aspect of the present invention is the above-described particles that are core particles for coating.

  According to the present invention, it has become possible to provide core particles for coating containing a drug having an unpleasant taste such as a bitter taste in a high concentration.

  The “particle” in the present invention contains a drug having an unpleasant taste such as a bitter taste in a high concentration, and is mainly used as a core particle for coating. For example, 35-50% by weight of ibuprofen, 3-6% by weight of light anhydrous silicic acid, 10-25% by weight of crystalline cellulose, 30-40% by weight of candy powder, and 5-15 of binder in the particles. The particles are characterized by containing mass%, having an average particle size of 175 to 300 μm, a geometric standard deviation of particle size distribution of 2.0 or less, and a friability of 5% or less. Alternatively, 35-50% by weight of ibuprofen, 3-6% by weight of light anhydrous silicic acid, 10-25% by weight of crystalline cellulose, 30-40% by weight of candy powder, and 0-15% by weight of binder. The powder is mixed, the obtained powder is fluidized in a rolling or stirring fluidized bed granulator, and the average particle diameter obtained by spraying the binding liquid is 175 to 300 μm, and the geometric standard deviation of the particle size distribution is 2 0.03 or less and a friability of 5% or less.

  “Unpleasant taste” includes, in addition to so-called bitter taste, astringent taste, pungent taste, and the like, and is not particularly limited as long as it is a taste that causes a deterioration in the feeling of administration by oral administration.

  “Drugs with an unpleasant taste” have an unpleasant taste such as a bitter taste, and an unpleasant presentation by adding several kinds of drugs in addition to a large amount per day as well as a small amount. The case where the compounding quantity of the drug which has a taste increases as a whole is also included. Examples of the compound having a large amount per day include ibuprofen, enzamid and acetaminophen. Examples of drugs having an unpleasant taste, although not much in themselves, include, for example, herbal extracts such as fennel oil, licorice extract, fennel extract, cinnamon oil, clove oil, belladonna extract, funnel extract, d -Chlorpheniramine maleate, L-aspartic acid, potassium L-aspartate, magnesium L-aspartate, L-isoleucine, L-glutamine, L-phenylalanine, L-methionine, L-histidine hydrochloride, ascorbic acid, aspirin, Sodium azulenesulfonate, aminoethylsulfonic acid, aldioxa, isopropylantipyrine, ursodeoxycholic acid, ergocalciferol, octothiamine, caffeine, guaifenesin, potassium guaiacolsulfonate, dipotassium glycyrrhizinate , Magnesium aluminate, Tocopherol succinate, Cholecalciferol, Sodium chondroitin sulfate, Salicylamide, Cyanocobalamin, Dibrofilin, Sucralfate, Semi-alkaline proteinase, Albumin tannate, Berberine tannate, Thiamine disulfide, Theophylline, Dehydrocholic acid, Tranexam Acid, nicotinamide, noscapine, retinol palmitate, calcium pantothenate, biotin, sodium picosulfate, bisacodyl, bisbutiamine, bisbenchamine, tipepidine hibenzate, dextromethorphan of phenolphthalate, cloperastine fendizoate, fumarate Cremastine acid, ferrous fumarate, fursultiamine, bromvalerylurea, hesperidin Hepronicart, benfotiamine, carbinoxamine maleate, chlorpheniramine maleate, pheniramine maleate, mequitazine, magnesium aluminate metasilicate, methylmethionine sulfonium chloride (VU), isopropamide iodide, riboflavin, codeine phosphate, dihydrocodeine phosphate, Dimemorphan phosphate, pyridoxal phosphate, sodium riboflavin phosphate, calcium hydrogen phosphate, sodium benzoate caffeine, carnitine chloride, berberine chloride, arginine hydrochloride, istipendyl hydrochloride, cloperastine hydrochloride, chlorhexidine hydrochloride, dicyclomine hydrochloride, dicetiamine hydrochloride, diphenidol hydrochloride Diphenylpyraline hydrochloride, diphenhydramine hydrochloride, cetraxate hydrochloride, thiamine hydrochloride, Riprolysine, Trimethoquinol hydrochloride, Noscapine hydrochloride, Papaverine hydrochloride, Hydroxocobalamin hydrochloride, Pyridoxine hydrochloride, Phenylpropanolamine hydrochloride, Phenylephrine hydrochloride, Fursulfiamine hydrochloride, Bromhexine hydrochloride, Meclizine hydrochloride, Methoxyphenamine hydrochloride, Lanitidine hydrochloride, Lysine hydrochloride, Loperamide hydrochloride, dry aluminum hydroxide gel, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, bismuth subgallate, alimemazine tartrate, butyl scopolamine bromide, methyl atropine bromide, methyl octatropine bromide, methyl bena bromide Cutidium, scopolamine hydrobromide, dextromethorphan hydrobromide, thiamine nitrate, tocopherol acetate, hydroxocobalamin acetate, aluminum hydroxide and hydrogen carbonate Thorium coprecipitate, magnesium hydroxide, magnesium carbonate, sodium hydrogen carbonate, precipitated calcium carbonate, sodium copper chlorophyllin, calcium lactate, anhydrous caffeine, folic acid, and a riboflavin butyrate. The content (formulation) of the drug having an unpleasant taste in the particles is usually 35% by mass or more, preferably 35 to 50% by mass, and more preferably 35 to 45% by mass. If it is less than 35% by mass, it is not necessary to mask the unpleasant taste until the coating core particles are prepared, and if it exceeds 50% by mass, it is difficult to prepare particles having physical properties suitable for coating.

  “Silicon dioxide” is formulated for the purpose of preventing aggregation of particles during granulation when a low-melting-point drug such as ibuprofen is adopted as a drug having an unpleasant taste. Even when blended, it has a function as a fluidizing agent. Examples of silicon dioxide include light anhydrous silicic acid and hydrous silicon dioxide. The light anhydrous silicic acid may be used alone or in combination.

  The content (blending) amount of silicon dioxide in the particles depends on the physical properties of the drug having an unpleasant taste and varies depending on the blending amount, but is usually 1 to 10% by mass, and 3 to 6% by mass. preferable. If it is less than 1% by mass, it will not even function as a fluidizing agent, and if it exceeds 10% by mass, it will not particularly contribute to the prevention of aggregation, and the bulk of the powder before granulation will become too large, making it difficult to handle. It is because it is not preferable.

  “Hygroscopic polymer” is a polymer compound that absorbs moisture, and is a fiber-based excipient used in the field of solid preparations, or a sugar such as glucose, mannose, or galactose in the structure. This includes a high molecular compound having a property of swelling when added with water. Examples of fibrous excipients include crystalline cellulose, starch derivatives such as sodium carboxymethyl starch and hydroxypropyl starch, and cellulose derivatives such as low-substituted hydroxypropylcellulose, croscarmellose and croscarmellose sodium. Can be mentioned. These may be used alone or in combination of two or more.

  The hygroscopic polymer is blended in order to keep the operating moisture value during granulation at 10 to 20%. If the operating moisture value is less than 10%, particles are not formed, or even if formed, the particles are brittle, and it is not preferable because particles having a strength that can withstand coating cannot be obtained. On the other hand, if the operating moisture value exceeds 20%, the granulation proceeds at a stretch, which may cause agglomeration or lumps, which is not preferable.

  The operating moisture value here is expressed as a weight loss (%) when sampling wet granules (wet bodies) during granulation and heating 10 g at 70 ° C. for 30 minutes.

  The content (formulation) of the hygroscopic polymer in the particles differs depending on how much water is used (sprayed) and at what ratio in the granulation. It is mass%, and 10-25 mass% is preferable. When it is less than 5% by mass, it becomes difficult to keep the operating moisture value within a certain range, and when it exceeds 30% by mass, the purpose of the present invention is to contain a drug having an unpleasant taste at a high concentration. Because it is done.

  The “saccharide excipient” in the present invention has a solubility in water at 20 ° C., that is, a value of solute / (solute + solvent) × 100 is 30% by mass or more, preferably 30-80% by mass, more preferably It is a saccharide that is 40 to 75% by mass (see “Monthly Food Chemical”, Food Chemistry Newspaper, p. 20-21, published September 1999). It is an indispensable substance that dissolves in water and develops stickiness, solidifies and contributes to the formation of particles and enhancement of its strength. Without this, let's devise a manufacturing method to increase the amount of binder High-strength particles that can withstand the coating could not be prepared. Examples of such saccharide-based excipients include candy powder (Maltose Syrup Powder), powdered sugar, erythritol, xylitol, sorbitol, maltitol, lactitol, sucrose, anhydrous maltose, and hydrous maltose. In addition to these, two or more may be used in combination.

  The content (formulation) of the saccharide-based excipient in the particles is usually 10 to 50% by mass, preferably 30 to 40% by mass, and more preferably 30 to 35% by mass. If the amount is less than 10% by mass, the particles are brittle and cannot withstand coating, and even if added in excess of 50% by mass, it does not particularly contribute to an increase in particle strength. It is not preferable to incinerate. The saccharide-based excipient may be blended in the powder before granulation, but a part thereof may be dissolved in a binding solution as a binder.

  The “binder” is blended for the purpose of solid crosslinking in order to obtain a certain particle size. Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol and starch, and these may be used alone or in combination of two or more.

  The content (blending) amount of the binder in the particles is usually 5 to 20% by mass, and preferably 5 to 15% by mass. The binder may be blended in the granulating powder, but it may be dissolved in water to form a binding liquid and sprayed on the granulating powder. Of course, you may make it mix | blend with both the powder for granulation, and binding liquid. In order to form solid crosslinks, it is better to use a binding solution.

  “Binding liquid” refers to water, an organic solvent, or a mixture of water and an organic solvent in which a binder is not dissolved or dissolved. In the rolling (stirring) fluidized bed granulation, the powder flowing in the apparatus is sprayed and used. If the amount of a solvent such as water is small relative to the binder, the concentration of the binder increases, which is not preferable because an excessive load is applied to the pump during spraying. If the amount of the solvent such as water is too much with respect to the binder, it takes time for granulation, which is not preferable because the working time becomes long. Usually, a binding solution of 5 to 10% by mass is used.

  The “mean particle diameter” in the present invention is a mass average diameter. Specifically, the sampled particles (for example, 5 g) are 30M (500 μm), 42M (355 μm), 60M (250 μm), 80M (180 μm), 100M (150 μm), 150M (106 μm), 200M (75 μm), and 270M. (53 μm) placed on a sieve stacked in order, classified by applying vibration for a certain time (for example, 3 minutes), 30M sieve residue, 42M sieve residue, 60M sieve residue, 80M sieve residue, 100M sieve residue, 150M sieve residue , 200M sieve residue, 270M sieve residue and 270M passage mass is measured. Multiply each mass by the median value of the particle size classification between each sieve that has been calculated in advance, and obtain the mass average diameter obtained by dividing the sum by the total mass (5 g), that is, the average particle size in the present invention. is there. For example, it can be automatically measured by using a robot shifter (seishin corporation). M represents a mesh.

  In the case of granules such as powders and granules, the average particle size is 100 to 100, considering that it is easy to take and two or more types of granules having different main ingredient components are prepared and mixed to ensure uniformity. It is preferably in the range of 400 μm (see Non-Patent Document 2). The average particle diameter is preferably 100 to 400 μm, considering that the particles of the present invention are also coated and formulated as a granule such as a powder having excellent dosing and mixing uniformity. More preferably, it is -350 micrometers, and it is further more preferable that it is 200-300 micrometers. In addition, small particles are preferable, but particles with a particle size of less than 100 μm have a large specific surface area, which requires a large amount of coating liquid for coating and is uneconomical. This is the reason why it is often 100 μm or more, and it is difficult to ensure manufacturing suitability.

  “Particle size distribution (particle size distribution)” refers to the ratio of particles belonging to a certain particle size range to the total amount of powder. Specifically, the particles (for example, 5 g) sampled in the same manner as described above are 30M (500 μm), 42M (355 μm), 60M (250 μm), 80M (180 μm), 100M (150 μm), 150M (106 μm), 200M ( 75 μm) and 270 M (53 μm) in order, placed on sieves in order, classified by applying vibration for a certain time (for example, 3 minutes), 30 M sieve residue, 42 M sieve residue, 60 M sieve residue, 80 M sieve residue, 100 M sieve residue , 150M sieve residue, 200M sieve residue, 270M sieve residue and 270M passage mass are measured. Each mass is divided by the total mass (5 g) and multiplied by 100 and expressed in mass%. Considering the use as a core particle for coating, the “geometric standard deviation” is usually 2.0 or less, preferably 1.7 or less, and more preferably 1.5 or less. Here, the geometric standard deviation is obtained by dividing the particle diameter when the cumulative passage fraction is 84.13% obtained by the logarithmic normal distribution by the particle diameter (median diameter or geometric mean diameter) when the cumulative passage fraction is 50%. This is the value when

  The average particle size, particle size distribution, and geometric standard deviation depended on “Modern Chemical Engineering I” (1988, Asakura Shoten, p. 239 to p. 245) edited by the Japan Society for Chemical Engineering.

  “Bulk density” means adding a powder sample to a container with a known volume (for example, a cylindrical container with a diameter of 30 mm, 100 mL), scraping the surface of the powder, weighing it, and measuring the mass of the powder sample at this time. It is the value divided by the inner volume of the container. At this time, the container is not tapped. Also called apparent specific gravity.

In the present invention, the “bulk density” is measured by means of A.T. B. A D powder meter was used. Considering the use as the core particle for coating, the bulk density of the particle of the present invention is usually 400 g / dm ³ or more.

  “Wearing degree” is determined by filling 5 g of particles of 850 μm or less and two metal spheres having a diameter of 20 mm and a mass of 28 g into a cylindrical metal container (for example, a ball mill grinder) having a diameter of 32 mm and a height of 88 mm, and an amplitude of 15 mm. The increase in the proportion (%) of fine powder of 75 μm or less generated when vibrating for 1 minute at a frequency of 1500 times / minute. Specifically, the sample is classified with a 850 μm sieve, the residue of the sieve is removed, the sample that has passed through the 850 μm sieve is mixed, and the ratio (%) of the fine powder of 75 μm is measured. Next, 5 g of the sample that has passed through the 850 μm sieve is filled into a cylindrical stainless steel container (Beta Mill: manufactured by Mitsubishi Chemical Engineering) having a diameter of 32 mm and a height of 88 mm together with two stainless balls having a diameter of 20 mm and a mass of 28 g. The container is vibrated for 1 minute at an amplitude of 15 mm and a frequency of 1500 times / minute, and then the ratio (%) of fine powder of 75 μm or less is measured. The “friability” is determined as an increase in the ratio (%) of fine powder of 75 μm or less before and after measurement.

  Considering the use as the core particle for coating, the friability of the particle of the present invention is usually 7% or less, preferably 5% or less, more preferably 3% or less.

  As the “particle production method”, for example, a drug having an unpleasant taste such as ibuprofen, light anhydrous silicic acid, crystalline cellulose, and a saccharide-based excipient are mixed and pulverized to prepare a granulating powder. Rolling (stirring) the granulating powder into a rolling (stirring) fluidized bed granulator, spraying the granulating powder with a binding solution in which a binder is dissolved in water, drying, and classifying. And a method of preparing the intended coating core particles.

  The core particles thus obtained are filled and fluidized in a coating fluidized bed granulator, sprayed with a coating solution in which a coating base such as hydroxypropylmethylcellulose is dissolved in water, and masked by applying a film coating. As the coating base, in addition to hydroxypropylmethylcellulose, ethyl cellulose and polyvinyl acetal diethylaminoacetate can be used. As the solvent, in addition to water, an organic solvent such as ethanol, a mixed liquid of water and an organic solvent, or the like is used. It is done.

  In addition, other active ingredients and additives can be added to the particles as long as the effects of the present invention are not impaired.

  Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples.

Example 1
(1) Preparation of granulating powder Ibuprofen 450.0 g
Riboflavin 4.0g
Light anhydrous silicic acid 50.0g
Crystalline cellulose 200.0g
American powder 350.0g
After weighing the above components, they were mixed and pulverized to obtain a uniform granulating powder.

(2) Preparation of binding solution Hydroxypropylcellulose 75.0 g
1425.0 g of purified water
Hydroxypropyl cellulose was dissolved in purified water to obtain a binding solution.

(3) Preparation of particles The powder for granulation is filled in a rolling fluidized bed granulator multiplex (manufactured by POWREC), granulated while spraying the binding liquid, dried and classified with a 850 μm sieve, To obtain particles.

Example 2
(Powder for granulation)
Ibuprofen 450.0g
Riboflavin 4.0g
Light anhydrous silicic acid 50.0g
Crystalline cellulose 200.0g
Powdered sugar 350.0g
(Binding liquid)
Hydroxypropylcellulose 75.0g
1425.0 g of purified water
The above components were weighed to prepare a granulating powder and a binding solution, and particles were obtained according to Example 1.

Example 3
(Powder for granulation)
Ibuprofen 450.0g
Riboflavin 4.0g
Light anhydrous silicic acid 50.0g
Crystalline cellulose 200.0g
American powder 350.0g
(Binding liquid)
Hydroxypropylcellulose 90.0g
968.0 g of purified water
The above components were weighed to prepare a granulating powder and a binding solution, and particles were obtained according to Example 1.

Example 4
(Powder for granulation)
Ibuprofen 450.0g
Riboflavin 4.0g
Light anhydrous silicic acid 50.0g
Crystalline cellulose 200.0g
American powder 350.0g
(Binding liquid)
Hydroxypropylcellulose 90.0g
910.0 g of purified water
The above components were weighed to prepare a granulating powder and a binding solution, and particles were obtained according to Example 1.

Comparative Example 1
(Powder for granulation)
Ibuprofen 450.0g
Riboflavin 4.0g
Light anhydrous silicic acid 50.0g
Low substituted hydroxypropylcellulose 150.0g
Phosphoric acid-calcium hydrogen 500.0g
Hydroxypropylcellulose 65.0g
(Binding liquid)
Hydroxypropylcellulose 65.0g
1235.0 g of purified water
The above components were weighed to prepare a granulating powder and a binding solution, and particles were obtained according to Example 1.

Comparative Example 2
(Powder for granulation)
Ibuprofen 450.0g
Riboflavin 4.0g
Light anhydrous silicic acid 50.0g
Crystalline cellulose 200.0g
D-mannitol 350.0g
(Binding liquid)
Hydroxypropylcellulose 75.0g
1425.0 g of purified water
The above components were weighed to prepare a granulating powder and a binding solution, and particles were obtained according to Example 1.

Test example 1
The physical properties of the particles obtained in Examples 1 to 4 and Comparative Examples 1 and 2 were measured and listed in Table 1 below. The non-defective product yield is a yield of particles having a particle size distribution from 106 μm to 500 μm suitable for coating core particles. A sieving method was used to measure the particle size distribution.

  From Table 1, it was confirmed that the particles of the present invention have physical properties suitable for film coating core particles, that is, suitable average particle size, sharp particle size distribution, high particle strength, and heavyness. In particular, it has been found that the low friability and high strength stand out as an important and fundamental characteristic as a core particle for coating.

  According to the present invention, development of a solid preparation such as a powder containing a drug having an unpleasant taste such as ibuprofen in a high concentration, having a small particle size and easy to take is expected.

Claims (2)

35% by weight or more of ibuprofen , 3 to 6% by weight of silicon dioxide, 10 to 25% by weight of hygroscopic polymer, candy powder, powdered sugar, erythritol, xylitol, sorbitol, maltitol, lactitol, sucrose, anhydrous maltose and water content at least one saccharide-based excipients maltose 30-40 wt%, and a binding agent by mixing powder containing 0-15 wt%, the resulting powder rolling or agitation fluidized bed granulator In the particles, obtained by spraying the binder and spraying the binding solution, 35% by mass or more of ibuprofen, 3 to 6% by mass of silicon dioxide, 10 to 25% by mass of hygroscopic polymer, candy powder, powdered sugar , Erythritol, xylitol, sorbitol, maltitol, lactitol, sucrose, anhydrous maltose and hydrous maltose 30 to 40% by mass, 5 to 15% by mass of binder, average particle size of 100 to 400 μm, geometric standard deviation of particle size distribution is 2.0 or less, and friability is 5% or less particles to.   The particle according to claim 1, which is a core particle for coating.