JP2013184888A - Covered particle - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a covered particle prevented from uneven dissolution and collapse of a covering layer and having long-time sustained releasability caused by regulating the uniformity of the film thickness of the covering layer so as to be in a prescribed level or more.SOLUTION: A covered particle is obtained by covering a core particle having 50-5,000 μm of a median diameter with a hardly water-soluble covering layer containing 1-30 pts.mass of a triacylglycerol having 8-12C fatty acids and 1-30 pts.mass of calcium stearate based on the whole hardly water-soluble covering layer. Further, the covered particle may have a water-soluble covering layer.

Description

  The present invention relates to a coated particle that improves the film thickness uniformity of a coating layer and imparts a sustained release property for a long time.

In various fields such as food, feed, pharmaceuticals, quasi-drugs, and cosmetics, the granular materials used as raw materials are used to prevent deterioration due to contact with the outside air, moisture, or with each other, or to improve fluidity. In order to impart sustained release properties, masking properties, elution prevention properties, acid resistance, etc., it is widely practiced to coat the powder particles with some kind of coating agent.
For example, in the case of foods, feeds, pharmaceuticals, and the like, sustained release in the gastrointestinal tract can be imparted to the granules by coating the granules with a slightly water-soluble or water-insoluble coating agent. When the core granular material is a physiologically active ingredient, bioavailability is expected to be improved by gradually elution in the intestine by providing sustained release.
Here, “sustained release” means “a property of gradually releasing components”. When the physiologically active ingredient does not have sustained release and dissolves immediately after ingestion, the concentration of the physiologically active ingredient in the digestive tract rapidly increases immediately after ingestion and then decreases in a short time and returns to the normal level. On the other hand, when sustained release is imparted to the physiologically active ingredient, the physiologically active ingredient is gradually dissolved, and the physiologically active ingredient concentration can be maintained within a certain range for a long time. Since the absorption rate of components per hour in the stomach and intestinal tract is limited, even if the amount of components ingested is the same, the total amount of physiologically active components to be absorbed increases if they have sustained release properties.
Most of the absorption of ingested components is done in the intestine. Usually, the transfer of the stomach contents to the intestinal tract starts about 10 minutes after the meal, and the transfer to the duodenum is completed in 3 to 6 hours. Some bioactive ingredients are damaged by gastric acid, but long-term sustained release may be required to improve the absorption efficiency by transferring such bioactive ingredients to the intestine with little damage. is there.
The time required from ingestion to excretion is about 24 to 36 hours. For this reason, if the sustained release property of the physiologically active ingredient is too long, it may be excreted without being completely eluted, and therefore it is considered that the time required for complete dissolution is preferably about 12 to 24 hours.

As a powder coating technique, there are a method of coating core particles with molten oil or powdered fat, a method of granulating and coating powder with water-containing alcohol-soluble protein such as zein (Patent Document 1), etc. Are known.
These technologies granulate and coat the core powder with fats and oils or poorly water-soluble substances to suppress elution of the core particles in the oral cavity or digestive tract, masking an unpleasant taste and sustained release. The purpose is to give sex.
Since the above-mentioned conventional technology has a process in which the core powder is coated while being granulated, the film thickness of the coated particles varies depending on the part, and the porous and non-uniform coated particles with many voids Become.
When these coated particles are taken into the living body, they are dissolved early from the thin part of the film or from the peripheral part of the voids by the moisture around the coated particle. The dissolution of the thin film portion and the peripheral portion of the void triggers the entire coated particle to elute early, making it difficult to impart sustained release properties for a long time.
For this reason, in the prior art, when it is desired to continuously exert the effect of the physiologically active ingredient, it is necessary to ingest several times a day, which is a burden on the ingestor.
In addition, some bioactive ingredients may be altered or deteriorated under acidic conditions, and these bioactive ingredients may be altered by the prior art coating before being transported to the intestines by early dissolution in the stomach. -It deteriorated and it was difficult to fully exhibit the said bioactivity effect.

Calcium stearate is widely used as a lubricant for the purpose of releasing tablets at the time of tableting, and it is also used for the purpose of preventing adhesion and coalescence of tablets during film coating and sugar coating processes (patented) Reference 2). However, no technique has been reported for inclusion in the coating layer of coated particles having a smaller particle size for the purpose of preventing coalescence.
The above-mentioned mold release action at the time of tableting with calcium stearate is due to the action of hindering the binding / adhesion of substances of calcium stearate itself, but when calcium stearate is blended in the particle coating layer as in the present invention The bonding and adhesion of substances in the coating layer may be hindered and the strength of the coating layer may be reduced. For this reason, conventionally, the addition of calcium stearate could not achieve both adhesion and coalescence prevention of the coated particles and maintenance of the strength of the coating layer.

  Patent Document 1 discloses a technique for coating a granulated product with a hydrous alcohol-soluble protein such as zein. In order to improve the uniform dissolution and dispersibility of the soluble protein in the coating solution, a plastic such as glycerin fatty acid ester is disclosed. Techniques using agents are described. The plasticizer is also added to the coating solution for the purpose of improving the flexibility and strength of the coating, but is not used for the purpose of suppressing adhesion between particles. In Patent Document 1, the adhesion and coalescence of particles are not a big problem because of the technique of originally coating while granulating the core particles. However, if adhesion and coalescence of particles occur, the uniformity of film thickness of the coating layer is impaired due to crushing during the process and peeling of the coating accompanying it, so glycerin fatty acid ester as in Patent Document 1 Depending on the addition of a plasticizer such as the above, the object of the present invention of improving the film thickness uniformity and imparting long-term sustained release could not be achieved.

  Patent Document 3 describes the composition of a coating agent for granular confectionery in which zein or shellac is dissolved. As a comparative example, an example in which medium chain fatty acid or glycerin fatty acid ester is added is shown. It has been shown that the use of the coating agent suppresses the adhesion between confectionery particles to some extent during the coating process, but in the case of coated particles with a small particle size as in the present invention, the adhesion between the particles is strong. In the same method as in Patent Document 3, adhesion between particles cannot be prevented.

JP-A-6-24963 JP 2008-24702 A JP-A-10-108630

  The problem to be solved by the present invention is to prevent the coating layer from being uniformly dissolved and disintegrated by making the coating layer thickness uniformity above a certain level, and to provide coated particles having a long-term sustained release property Is to provide.

As a result of intensive studies to solve the above problems, the inventors of the present invention greatly improve the film thickness uniformity of the coating by containing triacylglycerol having a fatty acid having a carbon chain length of 8 to 12 and calcium stearate in the coating solution. We have found that it has contributed and completed the present invention.
That is, the present invention includes the following inventions.
(1) Triacylglycerol having 1 to 30 parts by mass of a fatty acid having a carbon chain length of 8 to 12 and 1 to 30 parts by mass of a core particle having a median diameter of 50 to 5000 μm with respect to the total amount of the hardly water-soluble coating layer Coated particles obtained by coating with a poorly water-soluble coating layer containing calcium stearate.
(2) The coated particle according to (1), wherein the coating layer has a film thickness uniformity coefficient defined below, which is 0.2 or less.

Film thickness uniformity coefficient One coated particle is cleaved by a plane parallel to the major axis and parallel to the major axis of the fractured section, straight line A passing through the center of gravity and straight line B, perpendicular to straight line A, straight line A and 45 ° Are measured and calculated, and the average of the coefficient of variation of the five particles is defined as the film thickness uniformity coefficient.
(3) The coated particles according to (1) or (2), further having a water-soluble coating layer.
(4) The coated particle according to (3), wherein the outer layer of the poorly water-soluble coating layer has a water-soluble coating layer and further has the poorly water-soluble coating layer in the outer layer.

Since the coated particles obtained by the present invention have a uniform film thickness, they can prevent premature elution / disintegration from the thin film portion / void portion. That is, desired long-term sustained release property can be imparted to the coated particles by adjusting the film thickness of the coating layer while maintaining the film thickness uniformity of the coating layer.
This long-term sustained release can improve the absorption efficiency into the living body and reduce the number of daily intakes of the preparation.
In addition, even a physiologically active component that is altered or deteriorated under acidic conditions can be inhibited after being transferred to the intestine by suppressing alteration or deterioration under acidic conditions during retention in the stomach.

In the present invention, core particles having a median diameter of 50 to 5000 μm are used.
When a fine powder having an average particle size of less than 50 μm is used as a core particle, the particle size is too small to make a good coated particle. On the other hand, if the particle size exceeds 5000 μm, the powder particles will be damaged due to the load during the process, and thus good coated particles cannot be obtained. The particle diameter of the core particles is preferably 100 to 2000 μm, more preferably 150 to 1000 μm.
The particle size of the core particles is measured using a laser diffraction particle size distribution measuring device when the particle size is less than 1000 μm, and using a sieving method when the particle size is 1000 μm or more.
The core particle is the basis of the form of the entire coated particle, regardless of the presence or absence of a physiologically active component.
The component constituting the core particle may be any of various carrier substances that are usually used as a raw material for preparations, and examples thereof include reduced palatinose, cellulose, sucrose, and the like.

The coated particle of the present invention has a coating layer composed of a hardly water-soluble layer on the core particle, or a plurality of layers composed of repetitions of a slightly water-soluble layer and a water-soluble layer.
The poorly water-soluble coating layer in the present invention only needs to contain components that are poorly water-soluble at room temperature or insoluble in water and are used for food coating. Examples of this include zein, shellac, gluten, hardened fats and oils, fatty acid metal salts, and the like, but it is more preferable to use zein from the viewpoint of improving the film thickness uniformity.
Zein is a major component of corn protein and has the property of being sparingly water-soluble and soluble in hydrous alcohol. It can be said that it is suitable for forming a uniform film among the above-mentioned coating substrates because it can increase the solution concentration and has good film properties.
When zein is dissolved in hydrous alcohol, it is suitable to dissolve in 50 to 95 w / w%, preferably 60 to 80 w / w% hydrous ethanol. Zein does not dissolve if the ethanol concentration is too high or too low, which is not suitable.
The poorly water-soluble coating layer has a function of imparting sustained release properties to the coated particles, and may or may not contain a physiologically active component.
The total film thickness of the slightly water-soluble coating layer is preferably 10 μm to 500 μm, more preferably 15 μm to 100 μm. If it is too thin, the effect of elution may not be obtained for a long time, and if it is too thick, the physiologically active ingredient contained in the coated particles may be excreted outside the body before it is effectively eluted when ingested by the human body. is there.

The water-soluble coating layer in the present invention only needs to contain a water-soluble coating agent. Examples of the water-soluble coating agent include carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin, pullulan, xanthan gum, agar, curdlan, carrageenan, Examples include gum arabic, guar gum, gellan gum, pectin, and sodium alginate. Among them, hydroxypropylcellulose and hydroxypropylmethylcellulose are preferable.
Various additives can be contained in the water-soluble coating layer. Examples of the additive include water-soluble dyes, plasticizers such as glycerin and acylglycerol, and other additives generally used for film formation.
The water-soluble coating layer preferably contains a water-soluble or water-dispersible physiologically active component, and has a function of releasing the physiologically active component in vivo.

  Examples of physiologically active ingredients that can be incorporated into the core particles, poorly water-soluble coating layers, and water-soluble coating layers include water-soluble vitamins such as thiamine, ribabine, pyridoxine, cyanocobalamin, niacin, folic acid, pantothenic acid, biotin, and derivatives thereof, amino acids , Lactoferrin, citric acid, L-carnitine, collagen, hyaluronic acid, propolis, α-lipoic acid, CoQ10, plant extracts and the like.

From the above functions of the core particle, the water-soluble coating layer, and the poorly water-soluble coating layer, the following is possible as an embodiment of the present invention.
(1) Core particles-poorly water-soluble coating layer (single layer)
(2) Core particles-poorly water-soluble coating layer (multilayer)
(3) Core particle-water-soluble coating layer and / or poorly water-soluble coating layer (multilayer)
In any of (1) to (3), a physiologically active component can be contained in the core particle and / or the coating layer. In addition, in order to impart sustained release properties to the physiologically active ingredient, it is essential to coat it with a slightly water-soluble coating layer.
In a preferred embodiment, in order from the inner peripheral layer of the core particle not containing a physiologically active ingredient, (a) a water-soluble coating layer containing a physiologically active ingredient, (b) a poorly water-soluble coating layer, (c) a physiologically active ingredient And (d) sustained-release coated particles coated with a poorly water-soluble coating layer.
In another preferred embodiment, in order from the inner peripheral layer of the core particle containing the physiologically active ingredient, (a) a slightly water-soluble coating layer, (b) a water-soluble coating layer containing the physiologically active ingredient, (c) difficult Examples include sustained-release coated particles coated with a water-soluble coating layer.
The number of coating layers is not limited to the above-described preferred embodiment, and multiple layers can be stacked.

Triacylglycerol having a fatty acid having a carbon chain length of 8 to 12 contained in the poorly water-soluble coating layer is, for example, caprylic acid (carbon chain length 8), capric acid (carbon chain length 10), lauric acid (carbon chain length). 12) and the like, and medium-chain fatty acid triglycerides that are esters of glycerin.
Since glycerin has three hydroxyl groups that can contribute to an ester bond, various acylglycerols exist depending on the type of fatty acid and the binding site. The triacylglycerol having a fatty acid having a carbon chain length of 8 to 12 in the present invention does not limit the binding site of this fatty acid.
By adding triacylglycerol having a fatty acid having a carbon chain length of 8 to 12 to the poorly water-soluble coating in the present invention, the flexibility and adhesion of the coating is improved, and peeling of the coating during the process is prevented. A film having a uniform thickness can be formed.
Triacylglycerol having a long chain fatty acid having a carbon chain length of 14 or more has a high melting point and a high viscosity, so that the adhesion of the film becomes too high and the particles are likely to coalesce. It is unsuitable for inclusion in.

Calcium stearate only needs to satisfy the standards described in the Food Additives Official Standard or the Japanese Pharmacopoeia, and is mainly composed of stearic acid (a fatty acid having a carbon chain length of 18) and palmitic acid (a fatty acid having a carbon chain length of 16). It may be a calcium salt mixture of higher fatty acids.
By blending calcium stearate into the poorly water-soluble film in the present invention, coalescence of particles during the process can be prevented and the film thickness uniformity of the film can be improved.

The content of the triacylglycerol having a fatty acid having a carbon chain length of 8 to 12 in the poorly water-soluble coating layer is 1 to 30% by mass, preferably 3 to 20% by mass, based on the total amount of the hardly water-soluble coating layer. If it is less than 1% by mass, the effect of preventing film peeling cannot be obtained, and if it exceeds 30% by mass, the strength of the film tends to be impaired, which is not preferable.
The content of calcium stearate in the poorly water-soluble coating layer is 1 to 30% by mass, preferably 2 to 15% by mass with respect to the total amount of the poorly water-soluble coating layer. The effect of preventing the coalescence of the film cannot be obtained, and if it exceeds 30% by mass, the adhesion and strength of the film tend to be impaired.

In the present invention, the film thickness uniformity coefficient is an index indicating variations in film thickness, and the measurement method is as follows.
The coated particle is cut into two pieces. The cleaving method may use a razor blade, and if the particle size is small, a microtome may be used after embedding in a resin. Observed by electron microscope, straight line A parallel to the major axis of the fractured surface and passing through the center of gravity of the fractured surface, perpendicular to the straight line A, passing through the intersection of the straight line B and the straight lines A and B passing through the center of gravity of the fractured surface, and 45 ° with the straight line A A straight line C · D that intersects is defined. Measure and calculate the standard deviation of the film thickness at 8 points where each of the straight lines A, B, C, and D intersects the film, and calculate the coefficient of variation by dividing the obtained standard deviation by the average value of the film thickness at the 8 points. . The calculation method of the variation coefficient of the film thickness is as follows.

For the obtained coefficient of variation, the average of the five particles is defined as the film thickness uniformity coefficient.
The coated particles that are uniformly coated with the coating layer have a film thickness uniformity coefficient of 0.2 or less. However, in the case of particles in which two or more particles are repeatedly coalesced and peeled off by a load, a part of the film thickness becomes extremely thin or thick, and the film pressure uniformity coefficient increases. With the coated particles having a non-uniform film thickness, a part of the film dissolves at an early stage, and the expected sustained release property cannot be exhibited.

The coating method used in the present invention may be by an ordinary fluidized bed granulator, and by spraying the coating liquid on the granular material forming the fluidized bed by blowing from the lower part of the apparatus, A coating liquid containing a coating substance is attached to the periphery of the granular material and simultaneously dried by blowing from the lower part of the apparatus to form a coating layer. As the spray method, any of top spray, side spray, tangential spray, and the like may be used.
Here, the fluidized bed refers to a state in which the granular material moves in a certain range of height, balanced by floating by uniform air blowing from the lower part of the apparatus and dropping by gravity.
In order to improve the film thickness uniformity, it is necessary to improve the flexibility and spreadability of the coating and to prevent the particles from aggregating.
That is, the coating substance is not sprayed and adhered to the core substance, and is not completely fixed, but is spread by collision or rolling with the particles or the device wall, resulting in a denser coating. At this time, if the coating material lacks flexibility and spreadability, the coating does not spread and the coating peels off due to the load.
Further, when the particles are aggregated in the coating step, once the aggregated particles collapse due to the collision load between the particles or the apparatus wall, the coating is peeled off, and a uniform film thickness cannot be maintained.
In the present invention, 0.1-30 parts by mass of acylglycerol having a fatty acid having a carbon chain length of 8-12 and 0.1-30 parts by mass of calcium stearate are simultaneously contained in the sparingly water-soluble coating layer. It has the effect of improving the spreadability of materials and suppressing aggregation, and contributes to the improvement of film thickness uniformity.

  The coated particles of the present invention require the sustained release of physiologically active ingredients, and in various fields such as food, feed, pharmaceuticals, quasi drugs, veterinary drugs, cosmetics, etc., the coated particles can be used as they are or in various formulations. Can be used after processing.

EXAMPLES Hereinafter, although an Example demonstrates this invention, this invention is not limited by this.
In the following description, “%” is based on mass unless otherwise specified.
[Example 1]
600 g of palatinit (reduced palatinose: Mitsui Sugar Co., Ltd., particle size 16-22 mesh) was charged into a fluidized bed granulator (Freund Sangyo Co., Ltd., Spiraflow), and 145 g of coating liquid A was sprayed to coat. . Thereafter, 363.2 g of coating liquid B, 145 g of coating liquid A, and 363.2 g of coating liquid B were sprayed in this order to coat.
The composition of the coating liquid A is 4% riboflavin phosphate Na, 2% hydroxypropylcellulose (trade name “Selney L” manufactured by Nippon Soda Co., Ltd.), and 94% water.
The composition of the coating liquid B is as follows: zein (trade name “Kobayashi Zein DP” manufactured by Kobayashi Fragrance Co., Ltd.) 13.5%, medium chain fatty acid triglyceride (trade name “Panasate 810” manufactured by NOF Corporation, fatty acid composition: capryl Acid (carbon chain length 8) 85%, capric acid (carbon chain length 10) 15%) 1%, calcium stearate (manufactured by NOF Corporation) 0.5%, 70% ethanol 85%.
Table 1 shows the composition of the entire coated particles and the composition of each coating layer.

[Comparative Example 1]
The composition of the coating liquid B is as follows: zein (trade name “Kobayashi Zein DP”, Kobayashi Fragrance Co., Ltd.) 14%, medium chain fatty acid triglyceride (trade name “Panasate 810”, NOF Corporation) 1%, 70% ethanol Coated particles were obtained in the same manner as in Example 1 except that the content was 85%.
Table 1 shows the composition of the entire coated particles and the composition of each coating layer.
[Comparative Example 2]
The composition of the coating liquid B is 10% zein (trade name “Kobayashi Zein DP” manufactured by Kobayashi Fragrance Co., Ltd.), 5% medium chain fatty acid triglyceride (trade name “Panasate 810” manufactured by NOF Corporation), 70% ethanol. Coated particles were obtained in the same manner as in Example 1 except that the content was 85%.
Table 1 shows the composition of the entire coated particles and the composition of each coating layer.
[Comparative Example 3]
The composition of the coating liquid B is as follows: zein (trade name “Kobayashi Zein DP” manufactured by Kobayashi Fragrance Co., Ltd.) 14.5%, calcium stearate (manufactured by NOF Corporation) 0.5%, 70% ethanol 85%, The coated particles were obtained in the same manner as in Example 1 except that.
Table 2 shows the composition of the entire coated particles and the composition of each coating layer.
[Comparative Example 4]
The composition of the coating liquid B was 10% zein (trade name “Kobayashi Zein DP” manufactured by Kobayashi Fragrance Co., Ltd.), 5% calcium stearate (manufactured by NOF Corporation), and 70% ethanol 85%. Coated particles were obtained in the same manner as Example 1.
Table 2 shows the composition of the entire coated particles and the composition of each coating layer.
[Comparative Example 5]
Coated particles were obtained in the same manner as in Example 1 except that the composition of the coating liquid B was 15% zein (trade name “Kobayashi Zein DP” manufactured by Kobayashi Fragrance Co., Ltd.) and 70% ethanol 85%.
Table 2 shows the composition of the entire coated particles and the composition of each coating layer.
[Comparative Example 6]
Riboflavin phosphate Na 2.7% and starch (trade name “Pine Flow” Matsutani Chemical Industry Co., Ltd.) 97.3% mixed powder 600 g, fluidized bed granulator (Freund Sangyo Co., Ltd., Spiral flow) was sprayed and coated with 705.9 g of coating liquid (Zein (trade name “Kobayashi Zein DP”, Kobayashi Fragrance Co., Ltd.) 15%, 70% ethanol 85%).
The composition of the whole coated particle is shown in Table 3.

[Thickness uniformity coefficient]
About the coated granule obtained in Example 1 and Comparative Examples 1 to 6, the particles were cleaved with a razor blade under visual observation, and the straight line A and straight line parallel to the major axis of the fractured section and passing through the center of gravity of the fractured section by electron microscope observation A straight line C · D that intersects with the straight line B and passes through the intersection of the straight lines A and B perpendicular to A and intersects the straight line A and 45 ° is defined. The coefficient of variation of film thickness at 8 points where the straight lines A, B, C, and D intersect with the film were measured and calculated. The film thickness uniformity coefficient was calculated based on the film thickness variation coefficient obtained for 5 particles. Tables 4 and 5 show the film thickness measurement values, film thickness average values, standard deviation, film thickness variation coefficient, film thickness uniformity coefficient, and average film thickness for each particle.
[Average film thickness]
It was set as the average of the film thickness about 8 points | pieces and 5 particle | grains measured by said [film thickness uniformity coefficient].
[Elution test]
About the coated granule obtained in Example 1 and Comparative Examples 1-6, the elution test was done on condition of the following based on the Japanese Pharmacopoeia elution test method.
Eluent: Japanese Pharmacopoeia Disintegration Test Method Second Solution (pH 6.8)
Test method: Japanese Pharmacopoeia dissolution test paddle method Rotation speed: 100rpm
Temperature: 37 ° C
Test sample: Riboflavin phosphate Na equivalent to 30 mg Measurement method: Automatic dissolution tester (absorbance measurement at a wavelength of 266 nm)

  From Table 4, in Example 1 in which a triacylglycerol having a fatty acid having a carbon chain length of 8 to 12 and calcium stearate were contained in a slightly water-soluble coating layer, the coated granule having a uniform film thickness and good elution performance It turns out that was obtained. It can be seen that even after 3 hours and 12 hours have passed, the dissolution test does not completely dissolve and has a sustained release property for a long time.

In Comparative Example 1, the poorly water-soluble coating layer does not contain calcium stearate. The average film thickness is almost the same as in Example 1, but the film thickness uniformity coefficient is as high as 0.29, has a non-uniform coating layer, and the long-term sustained release is inferior to that in Example 1. ing.
In Comparative Example 2, the poorly water-soluble coating layer does not contain calcium stearate and contains 33.3% triacylglycerol, but does not contain calcium stearate and contains too much triacylglycerol, The coating layer becomes uneven and brittle, and does not have long-term sustained release properties.
From Table 5, in Comparative Example 3 containing 33.33% calcium stearate and containing no triacylglycerol having a fatty acid having a carbon chain length of 8 to 12 in the poorly water-soluble coating layer, the spreadability and flexibility of the coating layer Is a low and non-uniform coating layer and does not have a prolonged release property.
In Comparative Example 4, the poorly water-soluble coating layer contains 33.3% of triacylglycerol having a fatty acid having a carbon chain length of 8 to 12, but too much acylglycerol causes adhesion between coated particles in the process.・ Much coalescence and crushing are observed, resulting in a non-uniform coating layer and no prolonged release.
In Comparative Example 5, the poorly water-soluble coating layer does not contain both triacylglycerol and calcium stearate having a fatty acid having a carbon chain length of 8 to 12, but the coating layer has low spreadability and flexibility, and particles It becomes a non-uniform coating layer due to adhesion, coalescence and crushing of the material, and does not have a sustained release property for a long time.
In Comparative Example 6 of Table 3 according to the prior art, the elution test has already been completely dissolved at the time point of 3 hours, and does not have a long-term sustained release property.

Claims (4)

  1 to 30 parts by mass of triacylglycerol having a fatty acid having a carbon chain length of 8 to 12 and 1 to 30 parts by mass of calcium stearate with respect to the total amount of the hardly water-soluble coating layer. Coated particles obtained by coating with a poorly water-soluble coating layer containing The coated particles according to claim 1, wherein the coating layer has a film thickness uniformity coefficient defined below, which is 0.2 or less.

Film thickness uniformity coefficient One coated particle is cleaved by a plane parallel to the major axis and parallel to the major axis of the fractured section, straight line A passing through the center of gravity and straight line B, perpendicular to straight line A, straight line A and 45 ° Are measured and calculated, and the average of the coefficient of variation of the five particles is defined as the film thickness uniformity coefficient.   The coated particle according to claim 1, further comprising a water-soluble coating layer. The coated particle according to claim 3, wherein the outer layer of the poorly water-soluble coating layer has a water-soluble coating layer, and further has the poorly water-soluble coating layer in the outer layer.