JP2001213890A - Trehalose particles - Google Patents

Abstract

(57) Abstract: PROBLEM TO BE SOLVED: To provide trehalose particles having good flowability and sufficient compression moldability. SOLUTION: The purity is 99.0% or more and the average particle size is 10%.
３５０350 μm, apparent specific volume 1.2-2.5 cm ³ /
g, trehalose particles having a tablet hardness of 30N or more of a columnar molded product having a compression degree of 40% or less and a bottom area of 1 cm ² obtained by compressing 0.5 g at 50 MPa.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to trehalose particles having good fluidity and excellent compressibility in pharmaceutical applications.

[0002]

2. Description of the Related Art The hardness of tablets is required not to be chipped or worn during transportation, so that the higher the extrudability of the excipient, the better. If the excipient has low compression moldability, the amount of the excipient must be increased, which causes inconvenience when the amount of active pharmaceutical ingredients is large or when the size is reduced from the viewpoint of easy taking. Regarding the use of trehalose as a binder for pharmaceuticals, for example, Japanese Unexamined Patent Publication (Kokai) No. 6-217716 discloses that trehalose exhibits better compression moldability than starch additives, controls the particle size of trehalose, or controls other additives. It is described that a mixture with an agent is granulated (rolling fluidized bed, fluidized bed granulation, etc.) or spray dried to be useful directly as an additive for tableting. According to this, since the compression moldability of trehalose is comparable to that of granulated lactose, the hardness for pharmaceutical tablets is not sufficient, and it is expected that problems such as wear of the tablets during transportation and transportation will occur.

[0003] In addition, the publication discloses usefulness for direct tableting by controlling the particle size, granulating a mixture with other additives (rolling fluidized bed, fluidized bed granulation, etc.) or spray drying. It is described that it can be a novel additive. However, among the trehalose obtained by these granulation operations, the physical properties of trehalose having high moldability and excellent fluidity have not been known. Also,
Japanese Unexamined Patent Publication (Kokai) No. 11-14004 discloses that powdered trehalose is obtained by spray drying, but there is no description about the physical properties of the obtained trehalose. Further, the present invention includes monosaccharides and disaccharides other than trehalose. Do not contain these. Further, Japanese Patent Application Laid-Open No.
No. 76 discloses that trehalose can be used as a pharmaceutical excipient, but there is no description other than purity of trehalose, and trehalose necessary for imparting a good balance of compression moldability and fluidity. The physical properties of the compound were not known.

[0004]

When trehalose is used as an excipient for pharmaceuticals, mainly as a binder, powder which affects handling, productivity, uniformity of drug content, etc., such as fluidity, especially in direct tableting method. It is required to provide physical properties and a tablet hardness that does not cause attrition during transportation. The present invention provides trehalose particles having good flowability and sufficient compression moldability in a wide range of fields such as pharmaceuticals, foods, cosmetics, and industrial products, particularly in the field of pharmaceuticals.

[0005]

Means for Solving the Problems As a result of various studies on the problems of the prior art, the present inventors have found that by controlling the physical properties of trehalose, the fluidity of trehalose can be improved and the compression moldability can be greatly improved. And succeeded in completing the present invention. That is, the present invention provides (1) a purity of 99.0% or more, an average particle diameter of 10 to 350 μm, an apparent specific volume of 1.2 to 2.5 cm ³ / g, and a degree of compression of 40.
% And a trehalose particle having a tablet hardness of 30 N or more of a columnar molded product having a bottom area of 1 cm ² obtained by compressing 0.5 g at 50 MPa, and (2) a pharmaceutical preparation containing the trehalose particle of (1).

[0006]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. The trehalose particles of the present invention can use α, α-trehalose, α, β-trehalose, β, β-trehalose as a raw material.
α-Trehalose is preferred. Trehalose has two types of anhydrides and dihydrates in the solid state.
Dihydrate is more preferable because it does not absorb moisture over time.
This can be determined by the appearance of a heat of fusion peak near 100 ° C. by DSC measurement. Trehalose, the raw material,
It is obtained by enzymatic treatment of a starch decomposition product having a degree of polymerization of glucose of 3 or more, and is, for example, a commercially available product ("Trehaose" (manufactured by Hayashibara Biological Research Institute)) or JP-A-7-1438.
No. 76, manufactured by a method using an enzyme from a starch hydrolyzate (such as a solution containing one or two or more reductive starch partial hydrolysates selected from a glucose polymerization degree of 3 or more, A non-reducing saccharide-forming enzyme having a trehalose structure at its terminal is acted on from one or more kinds of partially decomposed reducing starches selected from a glucose polymerization degree of 3 or more, followed by glucoamylase or α-glucosidase. Trehalose and contaminated saccharides, and subjected to column chromatography using a strongly acidic cation exchange resin to obtain a trehalose having an improved content.

The trehalose purity in the trehalose particles of the present invention is 99.0% or more. Further, the glucose content as an impurity is preferably less than 1.0%.
If the purity of trehalose is less than 99.0%, the reactivity with the pharmaceutically active ingredient tends to increase. High-purity trehalose is expected to function as a drug stabilizer, but it has not been known that the presence of a trace amount of glucose as an impurity significantly impairs drug stability. More preferably, the purity of trehalose is 99.
3% or more. Preferably, the glucose content is 0.5% or less. Particularly preferably, the glucose content is not more than 0.3%. It is preferable that the trehalose purity is as close to 100% and the glucose content as 0% as much as possible, but the yield is deteriorated and the cost is increased. .

[0008] The trehalose particles of the present invention must have an average particle size of 10 to 350 µm. If it is less than 10 μm, the adhesion and cohesion of the particles increases, the fluidity deteriorates, and the handling becomes poor due to dusting or the like.
If it exceeds m, there is a problem that the miscibility with the drug or other excipients deteriorates and segregation of the main drug occurs, which is not preferable. Preferably 20 to 250 μm, more preferably 20 to 1
50 μm. Further, the trehalose particles of the present invention need to have an apparent specific volume of 1.2 to 2.5 cm ³ / g. If it is less than 1.2 cm ³ / g, the granulated material is hard and the plastic deformability decreases, and the compression moldability decreases, which is not preferable. If it exceeds 2.5 cm ³ / g, it becomes undesirably bulky and fluidity decreases. The preferred range is 1.2 to 2.0c
m ³ / g. The degree of compression (100
X [(1 / apparent tapping specific volume)-(1 / apparent specific volume)] / (1 / apparent tapping specific volume)) is 40%
It is as follows. If it exceeds 40%, the fluidity becomes poor, and if an open feed shoe is used by the direct compression method, the tablet weight variation becomes large. Preferably 35% or less,
More preferably, it is 30% or less. Although the angle of repose is one of physical properties that directly show fluidity, the trehalose particles of the present invention have an angle of repose of 45 ° or less, preferably 42 ° or less, and more preferably 40 ° or less.

[0009] The trehalose particles of the present invention preferably have a sphericity of 0.6 or more. This is because the closer the sphericity is to 1, the better the fluidity is.
That is all. 0.5 g of trehalose particles of the present invention is 5 g
The tablet hardness of a cylindrical molded product having a bottom area of 1 cm ² obtained by compression at 0 MPa is 30 N or more. If it is less than 30 N, chipping and abrasion often occur during transportation, which is not practical and is not preferable. Preferably it is 40N or more. Since the trehalose particles of the present invention have practically sufficient compression moldability, they can be formulated without using other excipients. Trehalose, which has very good flowability in addition to moldability and has a good balance of both functions, has not been known. In other words, trehalose crystals or trehalose crystals granulated simply cannot provide moldability and fluidity in a well-balanced manner, and can be achieved only by controlling the trehalose crystals to the above-mentioned range.

[0010] As described above, the trehalose particles of the present invention provide fluidity,
Because of good compression moldability, it is possible to improve the handleability, productivity and content uniformity in tableting of pharmaceuticals, especially in direct tableting, and to impart tablet strength to the extent of preventing abrasion during transportation. There are advantages such as. The trehalose particles of the present invention are obtained by purifying the raw material trehalose as necessary to make the trehalose purity 99.0% or more.
Granulation through a step of dissolving or suspending in water, a hydrophilic solvent or a lipophilic solvent, or a mixture thereof, or granulation through a step of wetting with water, a hydrophilic solvent, a lipophilic solvent, or a mixture thereof Can be obtained. Among them, it is preferable to use water, a hydrophilic solvent or a mixture thereof.

The former granulation method includes, for example, spray drying using an atomizer of a disk type or a two-fluid nozzle type using air. The slurry concentration at the time of spray drying is preferably 5 to 50% by weight as a trehalose solid content. If the amount is less than 5% by weight, it is economically disadvantageous, and in addition, the expected fluidity cannot be obtained because the particles become smaller and the adhesion and cohesion increases, and the aggregation state of the particles becomes sparse and bulky. If it exceeds 50% by weight, the particles become too dense and the compression moldability deteriorates. Preferably it is 10 to 40% by weight. When the melting point of trehalose is dihydrate, the drying temperature is 97 ° C. (anhydrous crystal is 203 ° C.). The drying temperature referred to here is, for example, an outlet temperature in spray drying, and is a temperature at which the trehalose particles reach at the time of drying.

As the latter granulation method, a known wet granulation method, that is, a known method such as fluidized bed granulation, stirring granulation, stirring fluid granulation, tumbling fluid granulation, kneading and crushing granulation, or A method in which two or more of these methods are combined is exemplified. In these methods, water, a hydrophilic solvent or a lipophilic solvent,
Alternatively, they are wetted with a mixture thereof, but the degree of wetting varies depending on the granulation method and the solvent used. The case of water and a hydrophilic solvent will be described below. For example, in a fluidized-bed granulation method, it is preferable to wet with 20 to 250% by weight of water, a hydrophilic solvent, or a mixture thereof based on the trehalose solid content. If the content is less than 20% by weight, the agglomeration state of the particles becomes sparse and bulky, resulting in poor fluidity. If it exceeds 250% by weight, the particles become too dense and the compression moldability deteriorates. Preferably 50 to 150% by weight
It is. In the stirring granulation method and the kneading and crushing granulation method, it is preferable to wet with trehalose solid content of 1 to 80% by weight of water, a hydrophilic solvent, or a mixture thereof. If the amount is less than 1% by weight, the aggregation state of the particles becomes sparse and the particles become bulky, so that the fluidity becomes poor. If it exceeds 80% by weight, the particles become too dense and the compression moldability deteriorates, which is not preferable. Preferably it is 3 to 50% by weight.

[0013] After drying, a sizing step for controlling the particle size may be performed, if necessary. As a pretreatment for granulation, a pulverization step using a pulverization method such as a ball mill, a bead mill, a tube mill, and a vibration mill may be performed. After grinding and kneading, spheronization using a marmellaizer or the like is optional. For drying by the wet granulation method, a tray hot air dryer, a drum dryer, a belt dryer, a fluidized bed dryer, a tumbling fluidized bed dryer, or the like can be used. During grinding and kneading, it may be wetted with water, a hydrophilic solvent, or a mixture of both,
As the hydrophilic solvent, for example, methanol, ethanol, propanol, isopropanol, butyl alcohol, etc.
It is preferable to use one which is miscible with water such as lower alcohol having about 1 to 6 carbon atoms and water such as acetone, but hardly dissolves trehalose. These may be used alone or in combination of two or more, and particularly, methanol, ethanol, isopropyl alcohol, acetone and the like are preferable.

The pharmaceutical preparation according to the present invention is a step of mixing trehalose particles and the preparation components and then processing them into granules, tablets, or the like, or a wet powder in which the prepared granules are mixed with trehalose particles in a powder form to form tablets. It is obtained through a tableting step and the like, and is a solid preparation such as tablets, powders, fine granules, granules, dry extracts, dry syrups, capsules, and troches. These may be provided with a coating such as a sustained-release, a bitter mask and an enteric coating, if necessary. The trehalose particles of the present invention are useful for tablets among these pharmaceutical preparations, and particularly useful for tablets that improve the feeling of taking and that rapidly disintegrate in the oral cavity. The pharmaceutical preparation contains, in addition to the trehalose particles, a pharmaceutically active ingredient (which may be coated for the purpose of imparting sustained release, a bitter mask, enteric coating, etc.) and other additives as necessary. The content of the trehalose particles varies depending on the content of the medicinal ingredient, the physical properties of the target preparation, etc., but is 1 to 99.9% by weight in the preparation.
The degree is preferred. The content of trehalose particles is 1% by weight
If it is less than the above, the hardness and friability required for a pharmaceutical preparation cannot be imparted. If it exceeds 99.9% by weight, the content of the medicinal component cannot be ensured. Particularly preferably, it is about 10 to 80% by weight. More preferably, it is about 20 to 70% by weight. The active ingredient to be used may be in any form such as powder, crystal, oil, solution, etc., arrhythmic agent, antihypertensive agent, vasodilator, diuretic agent, antipyretic analgesic anti-inflammatory agent, anti-ulcer agent, gastrointestinal drug Orally administered drugs such as intestinal medicine, osteoporosis treatment, antitussive expectorant, antiasthmatic, antibacterial, pollakiuria, nutrient tonic, vitamin and the like. The medicinal component is used alone or in combination of two or more. Further, the present invention includes not only pharmaceuticals but also health foods, bath preparations, veterinary drugs, diagnostics, agricultural chemicals, fertilizers, and the like, which are used in the form of molded products.

The content of the medicinal component varies depending on the kind and properties of the medicinal component, but is about 0.1 to 99% by weight based on the preparation. If the amount is less than 0.1% by weight, no medicinal effect is exhibited in many cases, and if it exceeds 99% by weight, it becomes difficult to impart hardness. Preferably 0.1 to 95% by weight,
Particularly preferably, it is 0.1 to 90% by weight. As other additives, excipients, disintegrants, binders, lubricants, flavors, colorants, sweeteners, surfactants and the like can be freely added.

Examples of the excipient include celluloses such as crystalline cellulose and powdered cellulose, sugars such as sucrose, glucose, lactose, fructose and maltose, sugar alcohols such as mannitol, xylitol, maltitol, erythritol and sorbitol, and corn starch. And starches such as potato starch, and inorganics such as calcium hydrogen phosphate, calcium carbonate, silicic anhydride, hydrous silicic acid, aluminum silicate, calcium silicate, and magnesium aluminate silicate.

Examples of the disintegrant include celluloses such as croscarmellose sodium, carmellose calcium, carmellose and low-substituted hydroxypropylcellulose;
Starches such as sodium carboxymethyl starch, hydroxypropyl starch, partially pregelatinized starch, crospovidone and the like. As a binder,
Hydroxypropylcellulose, hydroxypropylmethylcellulose, celluloses such as methylcellulose,
Alpha starch, starches such as starch paste, polyvinylpyrrolidone, synthetic polymers such as carboxyvinyl polymer, sodium alginate, xanthan gum,
And natural polymers such as gum arabic.

Examples of the lubricant include magnesium stearate, calcium stearate, stearic acid, sucrose fatty acid ester, talc and the like. Examples of the aqueous solution of the coating agent include aqueous solutions of HPMC, HPC, PVP, polyvinyl alcohol, polyethylene glycol, and the like. As an aqueous suspension of the coating agent,
A water-insoluble coating agent in a suspended state, such as ethylcellulose (EC), hydroxypropylmethylcellulose phthalate, cellulose acetate phthalate, carboxymethylethylcellulose, cellulose acetate, cellulose acetate butyrate, hydroxypropylmethylcellulose acetate succinate, etc. Examples include aqueous suspensions of celluloses, acrylic copolymers, vinyl copolymers, gelac, silicone resins, and the like. These coating agents may be used alone or in combination of two or more.

Hereinafter, the present invention will be described in detail with reference to examples, but these do not limit the scope of the present invention. The methods for measuring the powder properties and the physical properties of the tablets in Examples and Comparative Examples are as follows. -Trehalose purity [%] In the following method, the water of crystallization is not included in the calculation, and the saccharide is calculated as an anhydride. (1) 1.0 g of a sample is accurately measured and dissolved in water to make exactly 100 cm ³ . (2) 20 μl of this solution is analyzed by liquid chromatography under the following operating conditions. (3) Peaks appear in the order of oligosaccharide, trehalose, and glucose. (4) The ratio of the trehalose or glucose peak area to the total peak area is determined by the automatic integration method. Trehalose purity (%) = (A2 / (A1 + A2 + A)
3)) × 100 Glucose content (%) = (A3 / (A1 + A2 + A)
3)) × 100 A1: Oligosaccharide peak area A2: Trehalose peak area A3: Glucose peak area Operating conditions Detector: Differential refractometer (ERC-7515B) Column: MCI-GEL CK04SS (Mitsubishi Chemical Corporation) Column temperature: 85 ° C Mobile phase: water Flow rate: 0.4 cm ³ / min

Average particle size [μm] 5 g of powder is sieve-opened 500 μm, 300 μm, 250 μm
m sieve, and sieve opening 150 μm, 75
The particles were sieved with an air jet sieve using sieves of 45 μm, 45 μm, 38 μm, and 32 μm, and the on-screen weight percentage [%] of each sieve was determined. The result was represented by the particle diameter when the cumulative weight percentage was 50%. -Apparent specific volume [cm ³ / g] A powder sample is roughly filled in a 100 cm ³ glass measuring cylinder using a quantitative feeder or the like over 2 to 3 minutes, and the upper surface of the powder layer is brushed with a soft brush. This is a value obtained by reading the volume of the leveled level and dividing it by the weight of the powder sample. The weight of the powder is appropriately determined so that the volume becomes about 70 to 100 cm ³ .

-Apparent tapping specific volume [cm ³ /
g] After measuring the apparent specific volume, tapping is performed by hand on a low-impact table such as a desk covered with a rubber plate. The tapping is performed by dropping the powder vertically from a height of several centimeters onto the table until the compaction of the powder layer stops. Divide the volume of the powder layer by the powder weight. -Degree of compression [%] It was obtained from the following equation. Compressibility = 100 × [(1 / apparent tapping specific volume) −
(1 / apparent specific volume)] / (1 / apparent tapping specific volume) Angle of repose [゜] Measured by Sugihara formula (Pharmaceutics 27, 260, 1965).・ Sphericity [-] The major axis and minor axis of each particle of 100 particles are obtained by an image analyzer (Imagehyper, manufactured by Interquest).
The sphericity was calculated by the following equation. Sphericity = particle minor axis / particle major axis

Tablet hardness [N] A powder sample of 0.50 g is precisely weighed and charged into a one-sided compression mold capable of preparing a columnar molded body having a bottom area of 1 cm ² , and compressed with a predetermined stress. Hold at this pressure for 10 seconds to prepare a tablet. A load is applied in the diameter direction of the tablet with a Schroingel hardness tester (Freund Sangyo Co., Ltd., 6D type), and is expressed as the load when broken. The number of repetitions is 10, and the number average is taken. -Disintegration time of the tablet in the oral cavity [sec] The time required for the tablet to completely disintegrate with saliva in the oral cavity is measured using three healthy adult males as subjects. Measure twice for each person,
The average of three individuals was used. -Tablet friability [%] Sample 2 using friability tester (Pharmatest)
The friability was expressed as a weight percentage from the change in tablet weight before and after the test under the conditions of 0 tablets, 25 rpm, and 4 minutes.

[0023]

Example 1 Commercially available trehalose dihydrate (trade name “Trehaose”, manufactured by Hayashibara Biochemical Laboratory, purity 98.9%)
Is purified by recrystallization, and a trehalose aqueous solution adjusted to a 10% concentration is spray-dried under the conditions of a flow rate of 3 L / hr, an inlet temperature of 150 ° C., an outlet temperature of 80 ° C., and a rotation speed of a spray machine of 25000 rpm, to give trehalose particles having an average particle diameter of 45 μm. Obtained. Table 1 shows the physical properties of the powder and the hardness and friability when tableted at 50 MPa.

[0024]

Example 2 Commercially available trehalose dihydrate (trade name "Trehaose", manufactured by Hayashibara Biochemical Laboratory, purity 98.9%)
Was purified by recrystallization from trehalose (purity 99.3).
%) To 300 g of water (10% by weight of trehalose).
%) And a fluidized bed dryer (inlet temperature 7
Drying was performed at 5 ° C. and an air flow rate of 30 m ³ / hr) until the outlet temperature reached 45 ° C. Sieved at 1410 μm, average particle size 144
μm trehalose particles were obtained. Powder properties and 50MP
Table 1 shows the hardness and friability when tableting was carried out in a.

[0025]

Example 3 Commercially available trehalose dihydrate (trade name "Trehaose", manufactured by Hayashibara Biochemical Laboratory, purity 98.9%)
Was purified by recrystallization, and dried at 105 ° C. for 4 hours to produce 80 g of anhydrous trehalose (purity: 99.5%).
40 g of ethanol was added to the mixture, and the mixture was ground with a raikai machine. During this time, 70 g of ethanol was added. Then, it was cast on a glass plate and dried in a tray hot air dryer (40 ° C.) for 24 hours, and sieved with a sieve size of 350 μm. The trehalose particles after drying are left at room temperature (25 ° C., 55% RH) for 3 days,
It was a dihydrate (the water value measured by the Karl Fischer method was 9.8%). Powder properties and 50M of sieved product
Table 1 shows the hardness and friability when tableting was performed at Pa.

[0026]

Example 4 Commercially available trehalose dihydrate (trade name "Trehaose", manufactured by Hayashibara Biochemical Laboratory, purity 98.9%)
Was purified by recrystallization, and then a bantam mill (rotation speed: 10
Trehalose (purity 9), crushed at 2,000 rpm, feed rate 5 kg / hr, screen opening 2.0 mmφ).
500 g of 9.4%, average particle size 70 μm) was charged into a fluidized bed granulator (manufactured by Powrex Co., Ltd., multiplex MP-01 type), and the inlet temperature was 75 ° C. and the flow rate was 20 to 50 m ³ / hr, and the amount was 20 g / hr. After adding 500 g at a speed of min,
The trehalose particles were obtained by drying until the outlet temperature reached 40 ° C. Table 1 shows the physical properties of the powder and the hardness and friability when tableted at 50 MPa.

[0027]

Example 5 600 g of the granulated product of Example 1, 300 g of L-ascorbic acid, 50 g of crystalline cellulose, and 50 g of corn starch were mixed in a plastic bag for 3 minutes, and magnesium stearate was added as a lubricant in an amount of 0.5%. % And slowly mixed for 30 seconds. A rotary tableting machine (manufactured by Kikusui Seisakusho, 0.2 g tablet, 12 punches, rotation speed 54 rpm)
m at a compression pressure of 80 MPa) to give tablets. Table 2 shows the physical properties of the mixed powder and the physical properties of the obtained tablet.

[0028]

Comparative Example 1 Commercially available trehalose dihydrate crystal (trade name “Trehaose”, manufactured by Hayashibara Biochemical Laboratory, purity 98.9)
%) And the hardness and friability when tableted at 50 MPa are shown in Table 1.

[0029]

Comparative Example 2 Commercially available trehalose dihydrate (trade name "Trehaose", manufactured by Hayashibara Biochemical Laboratory, purity 98.9%)
Was purified by recrystallization from trehalose dihydrate crystals (purity 99.3%) using a bantam mill (rotational speed 10,000 rpm).
m, feed amount 5 kg / hr, screen opening 2.0
mmφ) to obtain a pulverized product having an average particle size of 68 μm.
Table 1 shows the powder physical properties of the pulverized product and the hardness and friability when tableted at 50 MPa.

[0030]

Comparative Example 3 Commercially available trehalose dihydrate (trade name “Trehaose”, manufactured by Hayashibara Biochemical Laboratory, purity 98.9%)
Was purified by recrystallization, and a trehalose aqueous solution (purity: 99.3%) adjusted to a 3% concentration was spray-dried under the conditions of a flow rate of 3 L / hr, an inlet temperature of 190 ° C, an outlet temperature of 80 ° C, and a spray machine rotation number of 35,000 rpm. Average particle size 8μm
Was obtained. Table 1 shows the powder properties of the granulated product and the hardness and friability when tableted at 50 MPa.

[0031]

Comparative Example 4 Commercially available trehalose dihydrate (trade name “trehaose”, manufactured by Hayashibara Biochemical Laboratory, purity 98.9%)
Was purified by recrystallization from trehalose (purity 99.3).
%) To 300 g of water (90% by weight of trehalose).
%) While stirring and granulating for 10 minutes, followed by drying in a tray hot air dryer (60 ° C.). Thereafter, the mixture was sieved at 1410 μm to obtain a granulated product having an average particle size of 390 μm. Table 1 shows the powder physical properties of the granulated product and the hardness and friability when tableted at 50 MPa.

[0032]

Comparative Example 5 600 g of the granulated product of Comparative Example 2, 300 g of L-ascorbic acid, 50 g of crystalline cellulose, and 50 g of corn starch were mixed in a plastic bag for 3 minutes, and magnesium stearate was added as a lubricant in an amount of 0.5%. % And slowly mixed for 30 seconds. A rotary tableting machine (manufactured by Kikusui Seisakusho, 0.2 g tablet, 12 punches, rotation speed 54 rpm)
m at a compression pressure of 80 MPa) to give tablets. Table 2 shows the physical properties of the mixed powder and the physical properties of the obtained tablet.

[0033]

[Table 1]

[0034]

[Table 2]

[0035]

Industrial Applicability The trehalose particles of the present invention have excellent fluidity, and in particular, can improve handling and productivity at the time of direct tableting, and at the same time, have excellent compressibility. Tablets using this can be produced and transported. The hardness required during storage can be maintained.

Claims (2)

[Claims] (1) a purity of 99.0% or more and an average particle size of 10
３５０350 μm, apparent specific volume 1.2-2.5 cm ³ /
g, trehalose particles characterized by having a tablet hardness of 30 N or more of a columnar molded product having a compression degree of 40% or less and a bottom area of 1 cm ² obtained by compressing 0.5 g at 50 MPa. 2. A pharmaceutical preparation comprising the trehalose particles according to claim 1.