JPH06192113A - Method for granulating galenicals and solid pharmaceutical preparation - Google Patents

Abstract

PURPOSE:To obtain a heavy granulated substance having a high strength and sharp grain size distribution by granulating galenicals according to simple operation. CONSTITUTION:Galenical powder or an additive is tumbled in a tilted surface of a rotating body 6 by using a tumbling fluidized type granulator and a liquid such as water is then sprayed from a nozzle 15 thereon while fluidizing the galenical powder or additive with a gas stream of a gas fed from a pipe 14. Thereby, a granulated substance of the galenicals is obtained. The granulation of the galenical extract can be carried out by spraying the galenical extract while tumbling and simultaneously fluidizing the additive such as a binder or an excipient. The resultant granulated substance is utilized as a solid pharmaceutical preparation.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an industrially useful method for granulating a herbal medicine and a solid preparation which can granulate a herbal medicine easily and efficiently.

[0002]

2. Description of the Related Art In the field of formulation of foods and pharmaceuticals,
Crude drugs may be mixed as crude drug powder and / or crude drug extract. When a crude drug, particularly a crude drug extract having a high hygroscopicity, is sprayed and granulated, the drying speed is low, and thus smooth granulation is usually impaired.

Japanese Patent Publication No. 55-1 for the granulation method of crude drugs
2889 discloses a method in which an excipient is suspended and fluidized using a fluidized granulator, and a crude drug extract to which pregelatinized starch is added is sprayed for granulation. In addition, Sunada et al. Reported that a crude drug powder was suspended and flowed using a fluidized granulator, and a binder solution was sprayed for granulation (No. 27).
Annual Technical Discussion Meeting, "Granulation and its applied technology", 6th 1992
March 30, Arcadia Ichigaya).

However, in such a method, the granules are made to be bulky and have a broad particle size distribution because they are floated and granulated.

On the other hand, in Japanese Unexamined Patent Publication (Kokai) No. 2-300135, a mixture of Kampo extract powder and a water-absorbing additive is floated and swirled in hot air by using an apparatus described in Japanese Patent Publication No. 46-10878. However, a method of intermittently spraying water or an aqueous solution of a binder is disclosed. Further, JP-A-5-95988 discloses Japanese Patent Publication No. 46-10878, JP-A-63-205136 or JP-A-64.
There is disclosed a method of granulating in the same manner as above, using the apparatus described in Japanese Patent Publication No. -67249.

[0006] However, in such a method, it is necessary to intermittently spray water or the like on a mixture which is floating and swirling, using a fluidized bed granulator equipped with a stirrer on the fluidized bed.
Granulation operation is complicated. Furthermore, since the raw material extract powder requires a step of drying the extracted extract, the number of manufacturing steps is increased, which is disadvantageous for granulation of crude drugs. In addition, in these methods, since Kampo extract powder has high hygroscopicity,
Particles are easily blocked by spraying with water and the particle size distribution tends to be broad. Furthermore, the rolling characteristics and compaction characteristics of the floating swirl type fluidized bed granulation are not sufficiently reflected, and it is difficult to select appropriate operating conditions in order to obtain heavy granules [Ishihara Pharmatec Japan, Vol.
8, No. 6, 75-80 (1992)]. for that reason,
According to the conventional method, it is difficult to obtain a granulated product having a large bulk density, a sharp particle size distribution and high strength.

[0007]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to granulate a crude drug, which is capable of obtaining a granulated product having a heavy weight, a sharp particle size distribution and a high strength with a simple operation, And to provide a solid preparation containing the obtained granulated product.

Another object of the present invention is to provide a method for granulating a herbal medicine, which is capable of efficiently obtaining a granulated product having the above-mentioned excellent properties even with a Chinese herb extract powder having high hygroscopicity, and It is to provide a solid preparation containing the obtained granulated product.

[0009]

DISCLOSURE OF THE INVENTION As a result of various studies to achieve the above object, the present inventors have used a tumbling fluidized granulator having a rotary body attached to a conventional fluidized granulator, It was found that the target granulated product can be easily obtained by granulating while rolling and flowing the crude drug component, and completed the present invention.

That is, in the method of the present invention, the crude drug component is tumbled on the surface of the rotator and is flowed to be granulated to obtain a granule of a crude drug.

Further, the solid preparation of the present invention contains the granulated product obtained as described above.

In the present specification, "rolling" means rolling on the surface of a rotating body, and "fluid" means floating in an air stream like a fluidized bed.

Examples of the raw material containing the crude drug component include medicinal parts of animals and plants, cell contents, secretions, extracts or minerals. Raw materials include, for example, red squirrel, Asenyak, aniseed fruit, armature, gum arabic, aloe, anthracnose, fennel, turmeric, oak, eagle, ages, engakusaku, nemoku, ougi, ougon, ouakubaku, ouren, konjac, processed bush, scorpionfish, gadget. , Cascara sagrada, cuckoo, cuckoo, valerian, chamomile, calamus root, carocon, caronin, kankyo, licorice, agar,
Kyouko, Kokuku, Catalpa, Pheasant, Kyounin, Kukujin, Keigai, Keihi, Ketsumeishi, Kengoshi, Gentiana, Genoshoko, Kouka, Koujin, Kobushi, Kobay, Koboku, Gohoku, Gojitsu, Pepper,
Goshuyu, Gomin, Wheat Starch, Gobaishi, Rice Starch, Colombo, Conzulango, Psycho, Saishin,
Saffron, Sankirai, Hawthorn, Sanshin, Sanshuyu, Sanna, Sansho, Sanyaku, Zio, Digitalis, Sikon, Sisong, Jiriyu, Peonies, Shajin, Shazenshi, Chazensou, Juuyaku, Shuksha, Shoukyo, Shouzu, Shouma, Suisanyou, Seihi, Sekisakukon, sexan, senega, senkyu, senkoutsu, senso, centaurum grass, senna, senburi, sojutsu, sokuhaku, soyo, daisy ghetto, rhubarb, taiso, takusha, ginseng ginger, chimo, clove, chorei, chimpi, capsicum, toki , Spruce, spruce, corn starch, turmeric, tragacanth, animal gall (including Yutan),
Nantenjitsu, nigaki, carrot, fritillaria, bakumondou, honey, mint, hazelfish, potato starch, hange, hijah, juniper, juniper, betel nut, bukuro, bungrass, belladonnakon,
Bowie, Bowcon, Bowfu, Hop, Buttonpi, Homika, Borei, Maou, Macri, Menthol, Mokutsu,
Includes mokko, yakchi, yarappa, youbait, yokinin, ryukotsu, ryutan, ryokkyo, forsythia, rosin, rotkon and the like. The crude drug components contained in these crude drugs can be used alone or in combination of two or more.

Preferred raw materials include rhubarb, licorice,
Keihi, Engosaku, Borei, Fennel, Shuksha, Ryokyo, Zio, Sanshuyu, Sanyak, Takusha, Bukuro, Botanpi, Processed Bushi, Carrot,
It includes soup, koboku, chimpi, kobushi, ginkgo, tannin, peony, toki and senkyu.

The crude drug components used in the present invention include crude drug powder and crude drug extracts. The crude drug powder is obtained by cutting or crushing the whole crude drug of the above raw material into small pieces or lumps, or cutting crude drug that is roughly cut, cut into small pieces or shredded; whole crude drug or cutting crude drug is rough powder, middle powder, fine powder Alternatively, a fine powdered crude drug can be used.

The crude drug extract can be obtained by a conventional method, for example, by using an extraction solvent and extracting from the raw material at an appropriate temperature, for example, low temperature or heating. The extraction solvent can be appropriately selected according to the galenical components, for example,
Water; alcohols such as methanol, ethanol, propanol, isopropanol, butanol; hexane,
Aliphatic hydrocarbons such as heptane; alicyclic hydrocarbons such as cyclohexane; aromatic hydrocarbons such as benzene and toluene; ketones such as acetone and methyl ethyl ketone; ethers such as dioxane, diethyl ether, diisopropyl ether, tetrahydrofuran; Esters such as methyl acetate and ethyl acetate; mixed solvents thereof and the like can be used. As the extraction solvent, water, a hydrophilic solvent and a mixed solvent thereof are often used.

As the crude drug extract, the extracted liquid extract may be used as it is, or it may be diluted with an additive, water or the like, and can also be used as a concentrated extract obtained by concentrating the extracted extract. Further, the crude drug extract can be used as a powder of the crude drug extract which is powdered by spray drying, stirring granulation, etc., if necessary, with additives added. A liquid herbal extract is often sprayed during granulation. The crude drug extract powder may be sprayed as a solution or dispersion of water and / or an organic solvent, or may be directly subjected to granulation by rolling and flowing.

The crude drug component may be granulated by combining the crude drug powder or the crude drug extract powder and the crude drug extract. That is, the crude drug extract or the crude drug extract powder may be granulated by spraying the crude drug extract while rolling and flowing. In this case, the mixing ratio of the crude drug powder and the crude drug extract varies depending on the purpose of the preparation and is not particularly limited, but 0.01 to 5 parts by weight of the crude drug extract, preferably 0 in terms of dry extract, relative to 1 part by weight of the crude drug powder. ．
It is about 1 to 3 parts by weight.

In the method of the present invention, in addition to the crude drug component, a physiologically active drug component may be used in combination. Examples of the medicinal component include central nervous system drugs, cardiovascular drugs, respiratory drugs, digestive drugs, antibiotics and chemotherapeutic agents, metabolic drugs, vitamin drugs, antacids and minerals. To be

Examples of the central nervous system drugs include diazepam, idebenone, aspirin, ibubrofen, paracetamol, naproxen, piroxicam, diclofenac, indomethacin, sulindac, lorazepam,
Examples thereof include nitrazepam, phenytoin, acetaminophen, edenzamid, ketoprofen and caffeine.

Examples of the cardiovascular drug include vinpocetine, propranolol, methyldopa, dipyridamole, furosemide, triamterene, nifedipine, atenolol, spironolactone, metoprolol, pindolol, captopril, isosorbide nitrate and the like.

Respiratory drugs include, for example, amlexanox, dextromethorphan, theophylline, pseudoephedrine, salbutamol, guaifenicin and the like.

Examples of the digestive system drugs include benzimidazole drugs such as lansoprazole and omeprazole, dimethidine, ranitidine, pancreatin, bisacodyl, 5-aminosalicylic acid and sucralfate.

Antibiotics and chemotherapeutic agents include, for example:
Includes cephalexin, cefaclor, cefradine, amoxicillin, bivanpicillin, bacampicillin, dicloxacillin, erythromycin, erythromycin stearate, lincomycin, doxycycline, trimethoprim / sulfamethoxazole and the like.

Examples of the metabolic drugs include serrapeptase, lysozyme chloride, adenosine triphosphate,
Includes glypenclamide, potassium chloride, etc.

Examples of vitamin drugs include retinol acetate, retinol palmitate, vitamin A oil, liver oil, strong liver oil, ergocalciferol, cholecalciferol, d-α-tocopherol succinate, d succinate.
1-α-tocopherol, d1-α-tocopherol calcium succinate, d-α-tocopherol acetate, d1-α-tocopherol acetate, d-α-tocopherol,
d1-α-tocopherol, thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate ester salt, dicetiamine hydrochloride, fursultiamine hydrochloride, octothiamine, shicothiamine, bisbutyamine, fursultiamine, prosultiamine,
Benfotiamine, Flavin adenine dinucleotide sodium, Riboflavin, Riboflavin sodium phosphate, Riboflavin butyrate, Pyridoxine hydrochloride, Pyridoxal phosphate, Hydroxocobalamin hydrochloride, Hydroxocobalamin acetate, Cyanocobalamin, Hydroxocobalamin, Ascorbic acid, Calcium ascorbate, Sodium ascorbate , Nicotinic acid, nicotinic acid amide, panthenol, calcium pantothenate, sodium pantetonate, biotin, potassium aspartate
Examples include magnesium equivalent mixture, inositol hexanicotinate, ursodesoxycholic acid, L-cysteine hydrochloride, L-cysteine, orotic acid and the like.

Furthermore, examples of the medicinal component include drugs called medicinal components extracted from the above-mentioned raw materials, for example, sennosides from rhubarb and senna, and glycyryl lithinic acid from licorice.

When these medicinal components are used, 0.0001 to 50 parts by weight can be used per 1 part by weight of the crude drug component.

In the preferred granulation method, additives are used with the galenical ingredients. As the additive, various additives commonly used in the production of solid oral preparations can be used. Additives include, for example, excipients, binders,
It includes disintegrants, lubricants, coloring agents, flavoring agents and the like. These additives may be used alone or in combination of two or more. Of these additives, at least excipients, binders and disintegrants are often used.

Examples of the above-mentioned excipients include lactose, corn starch, sucrose, talc, crystalline cellulose, mannitol, light anhydrous silicic acid, aluminum silicate, magnesium carbonate, calcium carbonate, calcium phosphate, porous substances and the like. .

As the binder, for example, hydroxypropyl cellulose (hereinafter sometimes referred to as HPC),
Examples thereof include hydroxypropyl methyl cellulose, pregelatinized starch, partially pregelatinized starch, methyl cellulose, carboxymethyl cellulose, polyvinylpyrrolidone, pullulan, dextrin, gum arabic and gelatin.

Examples of the disintegrating agent include low-substituted hydroxypropyl cellulose, carboxymethyl cellulose calcium (hereinafter sometimes referred to as ECG), starches, croscarmellose, crospovidone and the like.

Examples of lubricants include magnesium stearate and calcium stearate, and examples of colorants include titanium oxide, red iron oxide,
Examples include caramel and tar dyes. Further, the corrigents include, for example, sweeteners and flavors.

When a crude drug powder is used as a crude drug component, the amount of the additive with respect to the crude drug powder varies depending on the properties of the crude drug powder and is not particularly limited, but is 0.01 to 100 parts by weight of the crude drug powder.
It is 12 parts by weight, preferably about 0.01 to 7 parts by weight.

When a crude drug extract powder is used as a crude drug component, the amount of the additive to the crude drug extract powder varies depending on the properties of the crude drug extract powder and is not particularly limited, but 0.01 to 100 parts by weight per 1 part by weight of the crude drug extract powder. Parts, preferably about 0.01 to 80 parts by weight.

When a crude drug extract is used as a crude drug component,
The amount of the additive to the crude drug extract varies depending on the properties of the crude drug extract and the concentration of the crude drug extract and is not particularly limited, but 0.01 to 20 parts by weight relative to 1 part by weight of the dry extract (excluding water of the crude drug extract) , Preferably 0.1-10
It is about part by weight. When spraying a crude drug extract,
The amount of the additive is 0.01 to 10 parts by weight, preferably 0.01 to 10 parts by weight with respect to 1 part by weight of the crude drug extract in terms of dry extract.
It is about 5 parts by weight.

Further, when an additive is used together with the crude drug powder and the crude drug extract, the ratio of the crude drug powder to the crude drug extract is 0.01 to 5 parts by weight per 1 part by weight of the crude drug powder, as in the above. Parts, preferably 0.1 to 3 parts by weight. The amount of the additive is not particularly limited because it varies depending on the blending ratio of the crude drug powder and the crude drug extract, but 0.01 to 10 parts by weight based on 1 part by weight of the total amount of the crude drug powder and the crude drug extract (as a dry extract), It is preferably about 0.01 to 5 parts by weight.

When the additives are used in combination, a granulation method can be adopted depending on the properties of the crude drug component. For example, when a crude drug powder or a crude drug extract powder is used, the crude drug powder or the crude drug extract powder may be tumbled and flown together with an additive in a heated air stream to granulate. When a crude drug extract is used, the crude drug extract may be sprayed while rolling and flowing the additive.
Further, when granulating by spraying a liquid while rolling and flowing the granules, a method of granulating by incorporating a galenical component into at least one of the granules and the liquid is also preferable.
In this case, the powder and granules contain the crude drug powder, the crude drug extract powder and the additive, and the liquid contains the crude drug extract, water and the organic solvent.

Such a method can be implemented in various ways, for example:
It can be performed in the following manner.

(1) A method of granulating by spraying a liquid containing at least one component selected from water, an organic solvent and a crude drug extract while rolling and flowing the crude drug powder.

(2) A method of granulating by spraying a liquid containing an additive while rolling and flowing the crude drug powder. This liquid may contain at least one component selected from water, an organic solvent, and a crude drug extract in addition to the additive.

(3) A method of granulating by spraying a liquid containing at least one component selected from water, an organic solvent, a herbal medicine extract and an additive while rolling and flowing the crude drug powder and the additive. In this method, water, which may contain a crude drug extract, an aqueous solution or dispersion of a binder is preferably sprayed.

(4) A method of spraying a liquid (preferably a crude drug extract) containing a crude drug powder and a crude drug extract while rolling and flowing the additive to granulate.

(5) A method of granulating by spraying a liquid (preferably an aqueous solution or a water dispersion) containing a crude drug extract and an additive while rolling and flowing the additive.

Preferred methods include the above (2) and (3).
The methods (4) and (5) are included.

In such a method, a herbal medicine extract or water is preferably used as the liquid. In addition, when the additive is sprayed, usually at least a binder or an excipient is often used. The liquid may be a solution or a dispersion. The concentration of the additive in the liquid can be appropriately selected depending on the type of solvent, the drying temperature and the like, but is usually 0.1 to 75% by weight, preferably 0.1 to 50% by weight.

According to the method of the present invention, a granulated product having an apparent specific volume (bulk density) suitable for a preparation can be obtained by the rolling compaction action. The apparent specific volume of granules of crude drugs is, for example, 0.5 to 2.5 ml / g, preferably 0.8 to
It is about 2.2 ml / g. Apparent specific volume of 0.5 ml /
When it is less than g, the granulated product becomes hard and heavy, and the compressibility by tableting is lowered, and when it exceeds 2.5 ml / g, the bulk is high and the packaging container when it is made into fine granules or granules. As the size increases, the amount filled into the die hole during tableting decreases, and the weight of the tablet cannot be increased.

In the method of the present invention, the crude drug component is granulated by rolling and flowing the component on the surface of the rotating body. Preferably, the galenical components and the like are rolled on the surface of the rotating body provided at the bottom of the casing,
The tumbled granules are fluidized by an air stream to granulate. In such a method of the present invention, the rotational force of the rotating rotating body allows the granular material to smoothly roll on the surface of the rotating body, and the rolling granular material floats in the air flow to form a fluidized bed. Form. Further, the floating particulate matter falls on the rotating body and rolls. Thus, the granular material is granulated by the circulating flow in which rolling and flow are repeated. Therefore, even when using a crude drug extract having a large hygroscopicity or adhesiveness, in the process of rolling in a spiral shape in the centrifugal direction on the surface of the rotating body, the density of the granular material is increased by the rolling consolidation effect, and the particles are sized, Since the surface becomes smooth, it is possible to efficiently produce a granulated product having a large bulk density and strength and a sharp particle size distribution. Further, the air flow can efficiently dry the granular material.

According to another method, the galenical component is tumbled along with the rotation of the rotating body having the ventilation part on the inner wall, and is made to flow by the air flow from the ventilation part for granulation. In another preferred method, the herbal medicine components and the like are rolled along the inner wall with the rotation of the rotary drum having the ventilation part, and are granulated by being caused to flow by the airflow from the ventilation part which is in contact with the granular material. . In this case, the rotating drum constitutes a rotating body. The rotary drum may have a polygonal vertical cross section, and may form a horizontal rotary body rotatable about a horizontal axis as a central axis, and a stirring means such as a baffle plate may be provided on the inner wall of the rotary drum. Good.

In such a method, the rotation of the rotary drum causes the granules of crude drug components and additives to be tumbled and granulated by the cascade motion along the inner wall of the rotary drum, and the rotary centrifugal rotation of the rotary drum. When lifted by force, the densification of rolling increases the density of the granules and the particles are sized. Therefore, a granulated product having a large bulk density and strength and a sharp particle size distribution can be efficiently produced. Further, by supplying air from the ventilation part into the rotary drum, the rolling granular material can be fluidized to form a complicated mixing / rolling / fluidized bed, and the granulated material can be efficiently manufactured. Moreover, the granular material can be efficiently dried by the air flow.

In the present invention, various tumbling fluidized granulators capable of rolling and flowing granular materials can be used. In such an apparatus, it is preferable that the rolling property of the powder can be secured by the rotating body rotatably arranged on the fluidized bed. Specifically, it is desirable that the surface of the rotator has a small number of air holes for flowing the powder, and more preferably, a device having no air holes on the surface of the rotator, such as a multiplex [manufactured by Paulec Co., Ltd.]. ] Are preferred.

In such a tumbling fluidized granulator, for example,
The crude drug component can be granulated as follows. Put powdered granules such as crude drug powder and additives in a tumbling fluidized granulator, and roll the granules while rotating the rotating body. While spraying liquids such as crude drug extracts, water and organic solvents, with additives added as necessary, introduce gas into the equipment to form a fluidized bed of powder and granulate while rolling. To do.

As the rotating body, a rotating body in which the central portion is raised in a substantially conical shape or a truncated cone shape, that is, a rotating body having an inclined surface inclined downward to the side about the rotation axis,
For example, a cone-shaped or truncated cone-shaped rotating body is preferably used. The inclined surface of the rotating body is not limited to the linear inclined surface, and may be a curved inclined surface curved inward in order to increase the contact area with the granular material. It is also preferable to provide a stirring means on the outer peripheral portion of the rotating body so as to carry out stirring rolling granulation together with rolling flow.

The stirring means is preferably composed of two or more stirring members radially extending along the circumferential direction on the outer peripheral portion of the rotating body. The stirring means may be connected to each other in the circumferential direction. In this case, the stirring member has the conical shape,
It is preferable to extend radially in a circumferential direction from a position deviated from the axis of the truncated cone-shaped rotating body.

In addition, the tip of the stirring means is brought close to the inner wall surface of the casing, and the stirring means is provided with at least an inclined portion in which the height of the front portion gradually decreases in the direction of rotation, and a substantially horizontal surface connected to this inclined portion. It is preferable that the flat portion is used because the granular material can be agitated and tumbled and granulated by the inclined portion, and the tumbling and sizing can be performed by the flat portion. In particular, in addition to the inclined portion and the flat portion, the stirring means is such that the height of the rear portion gradually decreases in the direction opposite to the rotation direction, and if necessary, the height of the rear portion of the subsequent stirring means is It is preferable to have a surface having an inverted trapezoidal cross section with an inclined portion connected to the inclined surface of the front portion. In this case, since the granular material can be rolled on the inclined surface of the rear part and smoothly guided to the inclined part of the subsequent stirring means, the stirring rolling granulation can be efficiently performed.

The rotation speed of the rotating body can be appropriately selected according to the diameter of the rotating body, the internal volume of the apparatus, the herbal medicine components, the properties of the additive or liquid, the density of the desired granulated product, and the like. The speed is, for example, 0.1 to 20 m / sec, preferably 1-1.
It is about 0 m.

The method of spraying the liquid is not particularly limited,
For example, a top spray sprayed from a nozzle at the top of the tumbling flow granulator and a tangential spray sprayed tangentially to the tumbling flow of the granular material can be used. The liquid can be sprayed from one or a plurality of two or more nozzles.

According to the top spray, as the rotating body rotates, the powdery particles and the air flow form a swirl flow toward the center of the rotating body, so that the ratio of the powdery particles floating above the nozzle can be reduced. At the same time, the rise of the powder or granules can be suppressed, and the contact efficiency between the powder or granules and the mist of the sprayed liquid can be increased. And by the rolling operation by the rotation of the rotating body,
Generation of coarse particles is suppressed, and a granulated product that is heavy and has a sharp particle size distribution can be efficiently generated.

Further, in the tangential spray, since the tumbling powdery particles can be intensively sprayed, the contact efficiency between the powdery particles and the sprayed liquid can be improved. With the tangential spray, the liquid can be sprayed from an appropriate place such as the lower part or the middle part of the device.

As the air stream for forming the fluidized bed, various gases such as nitrogen, helium and carbon dioxide can be used, but air is usually used in many cases. The temperature of the air flow can be appropriately selected depending on the type of the additive, the spray amount of the liquid, the type of the solvent, etc., but is usually 25 to 120 ° C.
It is preferably about 30 to 100 ° C.

The air flow rate can be appropriately selected according to the inner volume of the tumbling fluidized granulator, the amount of powder or granules and the amount of liquid sprayed. For example, the bottom sectional area of the tumbling fluidized granulator is 1 m ² Every minute,
It is 5 to 300 m ³ , preferably about 10 to 200 m ³ .

The air flow can be introduced from an appropriate place where an upward flow is formed, but in order to efficiently circulate the granular material tumbled on the surface of the rotating body to the fluidized bed, it is preferable that the outer peripheral edge portion of the inclined surface of the rotating body be covered. It is introduced from below. In this case, from the outer peripheral portion of the rotating body to the inside of the casing through the flow path between the bottom plate that is disposed at the bottom of the casing and has an opening in the center and the rotor that is rotatably disposed on the bottom plate. Introduce airflow,
Granules rolled on the surface of the rotating body may be fluidized.

After the spraying of the liquid is completed, it is efficient to dry the granulated product by using the air flow as it is.

When granulating a crude drug extract, the additive is put in a tumbling fluidized granulator, and the additive is tumbled and fluidized while rotating the rotating body. It can be granulated by spraying, rolling and flowing.

Further, in the case where the nozzle is a multi-tube type sheathed nozzle which is formed coaxially with the spray nozzle for spraying the liquid and is capable of supplying powdery particles, while rotating the rotating body, Liquid and powder may be supplied from the sheathed nozzle for granulation. When using such a sheathed nozzle, in the area where the mist of the sprayed liquid is dispersed,
The liquid and the granular material can be brought into contact with each other.

Further, an ordinary ventilation coating machine or an apparatus modified from this can be used as a rolling fluidized granulator. The granulation mechanism using this tumbling fluidized granulator allows powdered and granular materials such as crude drug components and additives contained in a rotating drum that can be rotated in the horizontal axis direction, etc., as the rotating drum rotates. Rolling granulation occurs due to the cascade movement that occurs. In this case, the granular material is rolling-granulated when falling due to the cascade motion, and when lifted by the rotational centrifugal force of the rotating rotary drum, the density of the granular material increases due to the rolling compaction action,
Since the particles are sized, it is possible to efficiently produce a granulated product having a large bulk density and strength and a sharp particle size distribution. Furthermore, by supplying air into the rotary drum from the ventilation part of the rotary drum that comes into contact with the powder and granules, the rolling particles are fluidized to form a complicated mixing / rolling / fluidized bed. A preferable granulated product can be efficiently produced. Moreover, the granular material can be efficiently dried by the air flow.

The rotation speed of the rotary drum can be appropriately selected according to the inner diameter of the rotary drum, the herbal ingredients, the properties of the additives and liquids, the desired density of the granulated product, and the like. The peripheral speed of the rotating drum is, for example, 0.05 to 20 m / sec, preferably 0.5.
It is about 5 m / sec.

The method of spraying the liquid is not particularly limited, but in the case of a powder or granular material that tilts and rolls and falls due to a cascade motion, the powder or granular material on the upstream side, preferably the upstream of the average height of the inclined surface of the powder or granular material. It is preferable to spray to the powder and granules. The number of spray nozzles varies depending on the size of the rotary drum, but is one or more than one.

As the air supply method, either a direct method of supplying air in the same co-current direction as the direction of spraying the liquid or a reverse method of supplying air in the countercurrent direction opposite to the spray direction of the liquid can be adopted. The reverse method is useful for making the granulated material more fluid, and the direct method is advantageous for rolling the granulated material. Furthermore, the air supply method may be intermittent or continuous, and the direct method and the reverse method may be combined.

After the spraying of the liquid is completed, it is efficient to dry the granulated product by utilizing the air flow as it is. In this case, the reverse method is preferable. The type and temperature of the gas to be supplied are the same as in the case of the tumbling fluidized granulator.

The granules of crude drugs obtained by the method of the present invention are preferably used as a solid preparation. This solid preparation is obtained by subjecting the granules obtained as described above to sieving, pulverization, etc., if necessary, and adding the additives as they are or as necessary, and by a conventional method, powders, fine granules. It may be a solid preparation such as an agent, granules, tablets and capsules.

The tumbling fluidized granulator preferably used in the present invention is a casing for accommodating the granular material and forming a fluidized bed, and a rotary rotatably arranged under the casing. A body, a ventilation means formed between the outer circumference of the rotating body and the casing, and having a flow path for restricting passage of the powdery particles, and a blowing means for supplying gas upward through the ventilation means. Is equipped with. The flow path of the ventilation means may be formed in the lower part of the inner surface of the rotating body, and may be formed in a flat part extending from the inclined part of the rotating body toward the inner wall of the casing, or between the outer periphery of the rotating body and the casing. It may be configured by a ventilation member having a ventilation hole provided in the.

The rolling fluidized granulator preferably used in the present invention will be described below with reference to the accompanying drawings.

FIG. 1 is a vertical sectional view showing an example of a rolling fluidized granulator. This rolling fluidized granulator has a cylindrical casing 1
The rotating body 6 is rotatably arranged in the lower part of the inside, and the nozzle 15 is arranged in the upper space in the casing 1.

The bottom plate 2 of the casing 1 has a flat plate portion 3 extending from the inner wall of the casing 1, and an inclined plate portion 4 formed in the central portion and inclined obliquely upward toward the axial direction of the rotating body 6, It is composed of a through hole 5 formed in the center.

The rotating body 6 is composed of the inclined plate portion 4 of the bottom plate 2.
Corresponding to the above, a hollow truncated cone-shaped rotating body 7 having an inclined surface inclined downwardly on the side, and a stirring means formed in the peripheral portion of the rotating body 7 radially or curved at predetermined intervals. And a plurality of stirring blades 8 as Further, a labyrinth passage 9 is formed between the inclined plate portion 4 of the bottom plate 2 and the rotary body 7.

The agitating blade 8 has an inverted trapezoidal cross section having a front inclined surface that descends in the rotational direction, a flat surface, and a rear inclined surface that descends in the direction opposite to the rotational direction. And the plurality of stirring blades 8 are circumferentially connected to each other via the flat portion. A predetermined clearance is formed between the stirring blade 8 and the flat plate portion 3 of the bottom plate 2.

At the lower part of the bottom plate 2, a through hole 5 of the bottom plate 2 is formed.
A mounting plate 10 having a hollow cylindrical portion 11 protruding from is attached. The rotating body 6 is rotated by a rotating shaft 12 that is rotatably inserted in the hollow portion of the tubular portion 11. That is, the end of the rotating shaft 12 rotated by a motor or the like is fixed to the rotating body 6 and is rotatably supported by the bearing 13 of the mounting plate 10.

Further, a pipe 14 for supplying gas is connected to the mounting plate 10. This pipe 1
The gas supplied from 4 communicates with the lower space of the bottom plate 2. Therefore, the gas is supplied into the casing 1 from the side of the rotating body 7 through the lower space of the bottom plate 2, the through hole 5, and the labyrinth flow passage 9.

The nozzle 15 is arranged downward in a position above the axis of the rotary body 6 in the upper space of the casing 1. Therefore, it is possible to suppress the accumulation of particulate matter in the central portion of the rotating body 6.

Above the nozzle 15 in the casing 1,
A bag filter 16 for separating the particulate matter and the gas is attached, and the gas separated by the filter 16 is discharged from an exhaust port 18 formed in a top plate 17 of the casing 1.

FIG. 2 is a schematic view showing another example of the rolling fluidized granulator. This device is different from that shown in FIG. 1 except that a plurality of vent holes 25 are formed in the inclined plate portion 24 of the bottom plate 22 and that the rotor body 27 of the rotor 26 is formed in a conical shape.
The device is basically the same as the device shown in FIG.

In such an apparatus, when the granular material is housed in the apparatus, the liquid is sprayed and the gas is introduced, the granular material rolls on the inclined surface of the main body of the rotary body and is flowed by the air flow. A spiral fluidized bed can be formed. Then, the rolling compaction action makes it possible to obtain a granulated product having the above-mentioned excellent properties. Further, when the rotating body is equipped with a stirring blade, a strong rolling compaction effect can be given together with stirring, so that the granulated product is heavier and has a higher strength and a narrow particle size distribution width.

In the above apparatus, the stirring blade is not always necessary. Further, the bottom plate is not always necessary, and a ventilation part having a ventilation hole for restricting passage of particulate matter is provided between the outer periphery of the rotating body and the inner wall of the casing, and a gas is upwardly passed through the ventilation hole of the ventilation part. May be blown.
In this case, the rotating body may be composed of a rotating body main body having an inclined surface such as a conical shape or a truncated cone shape, and a flat portion having a flat surface which is continuous with the rotating body main body and constitutes an outer peripheral portion. . The ventilation part can be composed of a wire mesh, a perforated plate, a slit, or the like. Further, the ventilation part is not limited to the horizontal direction, but may be formed in an inclined part that is arranged so as to be inclined between the outer periphery of the rotating body and the inner wall of the casing.

Further, a stirring blade as the stirring means,
You may combine with the fixed blade attached to the inner wall of a casing. In this case, the fixed blade is attached to the flat surface of the stirring means with a predetermined clearance. By combining the stirring means of the rotating body and the fixed blade, stirring rolling granulation can be performed on the inclined surface of the front part of the stirring means, and the granular material is sandwiched between the flat surface and the fixed blade to achieve compaction and compaction. Since the coarse particles can be crushed, the granulated product has higher strength and a sharp particle size distribution. The clearance between the flat surface of the stirring means and the fixed blade can be appropriately set to, for example, 5 to 15 mm depending on the desired size, density and particle size distribution width of the granulated product.

FIG. 3 is a schematic view showing still another example of the rolling fluidized granulator. In this device, the rotating body 36 is formed by a conical rotating body 37, a flat plate portion 38 extending from the outer periphery of the rotating body toward the inner wall of the casing 31, and the flat plate portion to prevent passage of powder particles. Multiple slits 39 to regulate
And the flat plate portion 38 and the casing 3
The structure is basically the same as that of the device shown in FIG. 1, except that a gap is formed between the inner wall of the first structure 1 and the inner wall of the first structure.

FIG. 4 is a schematic view showing another example of the rolling fluidized granulator. In this device, a part of a flat plate portion extending from the outer periphery of a conical rotary body 47 that constitutes the rotary body 46 toward the inner wall of the casing 41 has a ventilation member 48 such as a wire mesh or a perforated plate that restricts the passage of powder or granular material. The device is basically the same as the device shown in FIG. 3 except that it is formed by.

In the apparatus shown in FIGS. 3 and 4, when the air flow rate is high, the particulate matter floats and the rolling effect is inferior, but by reducing the air flow rate, the rotating body 37,
The rolling efficiency of the granular material due to the inclined surface of 47 can be increased, and the object of the present invention can be achieved. It should be noted that the shape of the casing is not limited to the cylindrical shape, as long as it has a smooth inner wall.

FIG. 5 is a schematic vertical sectional view showing still another example of the rolling fluidized granulator, and FIG. 6 is a sectional view taken along line VI-VI in FIG. This device is known as a ventilation type coating machine for coating particles (for example, Japanese Examined Patent Publication No. Sho 62).
-19134, Japanese Patent Publication No. 62-19135,
JP-B-63-29980, JP-A-3-5848, etc.). However, it is not known that an aeration type coating machine is useful for rolling fluidized granulation of crude drugs.

This apparatus comprises a rotary drum body 51 having a nine-sided cross section which constitutes a rotary body, a ventilation member 52 which constitutes nine inner surfaces of the rotation drum body, and a stirring means attached to the inner surface of each ventilation member. Baffle plate 53 as
And a spray nozzle 54 arranged in the rotary drum body 51. The ventilation member 52 has a ventilation hole that opens toward the inside of the rotary drum body 51 and that restricts the passage of the powder or granular material. Also, the baffle plate 53
On the inner wall of the rotary drum main body 51, regulates the uneven flow of the powder and granules and makes the flow of the powder and granules uniform. The spray nozzle 54 is attached to communicate with a spray arm 55 extending inside the rotary drum body 51.

Rotating drum body 51 with each side bulging outward
A gas flow path 56 is formed between the ventilation member 52 and the ventilation member 52.
This gas flow path communicates with the inside of the rotary drum main body 51 through the ventilation member 52. Both sides of the rotary drum main body 51 are squeezed into a circular cross section, one side portion is used as a powder and granule supply and granule discharge port 57, and the other side portion extends laterally and has a bearing. A hollow shaft 59 rotatably supported by 58 is attached. This hollow shaft 59
Rotates the rotary drum main body 51 and can be rotated by a motor or the like.

An air flow distributor (not shown) connected to a blower (not shown) for air supply / exhaust is provided on the bearing 58 side of the rotary drum main body 51. This airflow distributor
With the rotation of the rotary drum body 51, the air flow from the blower is distributed to the predetermined gas passages among the nine gas passages 56. That is, in this example, since the gas is introduced by the reverse method, as the rotary drum main body 51 rotates,
The nine gas flow paths 56 are switched one after another by the air flow distributor, and the rotary drum main body 51 is connected from the air supply port 60 at the bottom of the device.
It is supplied into the rotary drum main body 51 through the ventilation member 52 from the gas flow path 56 that has moved to the lower part. The airflow passes through the bed of the granular material and is discharged from the exhaust port 61 through the ventilation member 52 and the gas flow path 56 that have moved to the upper part of the rotary drum body 51.

Along with the rotation of the rotary drum main body 51, a granular material bed having an inclined surface lifted in the rotational direction is formed. In this example, as shown in FIG. 6, the liquid is sprayed from the spray nozzle 54 to the upstream side of the granular material bed, that is, the granular material bed on the side lifted by the rotation of the rotary drum body 51. .

Spray nozzle 54 for spraying liquid
Is attached to a spray arm 55 that communicates with a hollow tube 55a extending into the rotary drum body 51 through the hollow portion of the hollow shaft 59, and the spray arm 55 is axially movable back and forth. Therefore, adjustment and inspection of the spray nozzle 54 can be performed by extending the spray arm 55 to the takeout port 57.

In such an apparatus, when the granular material is housed in the rotary drum body and the liquid is sprayed and the gas is introduced, the granular material is lifted in the rotating direction while rolling, and falls in a cascade motion. As it is performed, it is fluidized by the air flow. Then, the rolling compaction action makes it possible to obtain a granulated product having the above-mentioned excellent properties. In addition, by providing the stirring means, a stirring and mixing effect occurs, and a granulated product having a sharper particle size distribution can be obtained.

In the above apparatus, the rotary drum may have a vertical sectional shape of polygonal shape or circular shape. When the vertical cross-sectional shape of the rotating drum is polygonal, the number of sides is 3 to 25, preferably about 5 to 15. Also,
The side shape of the rotating body is not limited to the conical type as shown in FIGS. 5 and 6, but may be an onion type, a peer type, an apple type, or the like. The tumbling fluidized granulator does not have to be a horizontal granulator having a rotary shaft extending in the horizontal axis direction, and may be an inclined granulator having a rotary shaft inclined. Further, the stirring means is not always necessary.

The ventilation member can be made of, for example, a fine metal wire mesh or a breathable sintered metal, depending on the particle size of the powder. Further, the opening ratio of the ventilation member can be selected in consideration of the degree of rolling and fluidized granulation. If the rotating drum body has a polygonal cross section, the ventilation member does not have to form all the inner walls,
The inner wall of the rotary drum main body may be constituted by an appropriate interval, for example, a ventilation member and a non-ventilation member which are alternately arranged.
One or two of the two inner walls are composed of ventilation members,
The other inner wall may be made of a non-ventilating member. The ventilation member is
Usually, it is often mounted at equal intervals. The area% of the ventilation member occupying the inner wall of the rotating drum main body can be selected according to the rolling efficiency and the flow efficiency of the granular material, and is usually 10 to 100%.
It is preferably about 20 to 60%.

The ventilation member is attached to the inner surface of the rotary drum main body, and it is not necessary to rotate it together with the rotary drum main body. A ventilation means having a ventilation hole, for example, a pipe-shaped ventilation means is provided from the air supply port / exhaust port or the bearing side. It may be installed by being inserted into the rotary drum body and embedded in the powder or granular material.

Further, when the gas is introduced by the direct method, a flow path switching means such as a switching damper is provided between the air flow distributor and the blower so that the air is supplied from the upper part of the rotary drum body and the lower part is supplied. It can also be exhausted from. The number of spray nozzles may be one or two or more depending on the size of the rotary drum body.

[0100]

EFFECTS OF THE INVENTION According to the method of the present invention, the galenical components are tumbled and fluidized on the surface of the rotator for granulation.
With a simple operation, it is possible to efficiently produce a granulated product having a heavy and sharp particle size distribution and high strength.

[0101]

The present invention will be described in more detail based on the following examples, but the invention is not intended to be limited to these examples.

In the examples and comparative examples, the evaluation method of the granulated product is as follows.

Apparent specific volume: 50 g of the granulated product was gradually filled in a 200 ml graduated cylinder, and then the height of the packed bed was read on a scale and evaluated in units of ml / g.

Particle size: 30 mesh (500 μm), 10
0 mesh (150 μm), 140 mesh (106 μ
m) and a 200-mesh (75 μm) standard sieve (inner diameter: 20 cmφ) are stacked, 50 g of the granulated product is placed in the uppermost sieve bottom, and after shaking for a certain period of time, the sieve top and the sieve bottom (200
The weight of the granulated product remaining after passing through the mesh) was measured, and the weight% of the granulated product by each sieve was calculated.

Example 1 200 g of light anhydrous silicic acid was placed in a tumbling fluidized granulator (manufactured by Powrex Co., Ltd., Multiplex MP-01 type), and a rotary disk provided with a rotating body having a truncated conical inclined surface. To 150
It was rotated at rpm (peripheral speed 1.2 m / sec). On the other hand, 2000 g of a 10% by weight water-extracted extract (200 g as a dry extract) obtained from 533.6 g of rhubarb and 133.4 g of liquorice was top-sprayed at a spray rate of 20 g / min, while rolling at a blast temperature of about 40 ° C. Let

After the spraying was completed, the granules were obtained by drying for 20 minutes while rolling and flowing. The apparent specific volume of the granulated product was 2.0 ml / g, and the particle size was as follows.

30 mesh residue: 3% 100 mesh residue: 86% 140 mesh residue: 1% 200 mesh residue: 7% 200 mesh passage: 3% Example 2 Anchusan 623g, corn starch 59g, ECG16.
2 g and 35.5 g of light anhydrous silicic acid were put into the tumbling fluidized granulator used in Example 1, and the tumbling disc was rotated at 300 rpm (peripheral speed 2.4 m / sec) to mix while rolling. The composition ratio of 623 g of Anchusan is 3 parts by weight of Keihi powder,
3 parts by weight of Engosaku, 3 parts by weight of borei, 2 parts by weight of fennel, 2 parts by weight of licorice, and 2 ends of shukusha
By weight, 1 part by weight of Ryokyo powder.

Further, water was sprayed with a top spray at a spray rate of 45 ml / min for 9 minutes while rolling and flowing at a blast temperature of about 60 ° C., and then the water extract extract 864 from Anchu-san.
g (23% concentration, 199.3 g as a dry extract) was sprayed at a spray rate of 96 g / min for 9 minutes, and then water was sprayed at a spray rate of 17
Sprayed at g / min for 7 minutes.

After all the spraying was completed, the granules containing the powder and the extract were obtained by drying for 38 minutes while rolling and flowing. The apparent specific volume of the granulated product was 2.1 ml / g, and the particle size was as follows.

30 mesh residue: 1% 100 mesh residue: 96% 140 mesh residue: 1% 200 mesh residue: 2% 200 mesh passage: 3% Example 3 160 g of dio powder, 80 g of sausage powder, 80 g of sanyaku powder, takusha powder. 80g, Bucurou powder 80
g, 80 g of peony powder, 26.6 g of cinnamon powder, 13.4 g of processed bush powder, 80 g of carrot powder, 36 g of pregelatinized starch, 1.4 g of light anhydrous silicic acid, 2.6 g of corn starch used in Example 1 Put in a fluidized granulator,
The turntable was rotated at 300 rpm (peripheral speed 2.4 m / sec) and mixed while rolling.

Further, while tumbling and flowing at a blowing temperature of about 60 ° C., a 5 wt% HPC aqueous solution was sprayed with a tangential spray at a spray rate of 50 ml / min for 10 minutes, and then dried while tumbling and flowing for 30 minutes. , A granulated product was obtained. The apparent specific volume of the granulated product was 1.6 ml / g, and the particle size was as follows.

30 mesh residue: 0% 100 mesh residue: 97% 140 mesh residue: 3% 200 mesh residue: 0% 200 mesh passage: 0% Example 4 59 g of light anhydrous silicic acid and 83 g of ECG are used in Example 1. It was put in the tumbling fluidized granulator, and the rotary disk was rotated at 300 rpm (peripheral speed 2.4 m / sec) to mix while rolling. On the other hand, 1938 g of water-extracted extract (water content 53%, dried extract 10
27g) was sprayed with a tangential spray of 5268g of a mixture of 294g of light anhydrous silicic acid, 147g of synthetic aluminum silicate, 122g of lactose and 2767g of water. In addition, the composition ratio of 5135 g of coarsely chopped Kosandou acid peony is: 4 parts by weight of soup, 3 parts by weight of koboku, 3 parts by weight of cock, 1 part by weight of kanzo, 2 parts by weight of kobushi, 2 parts by weight of ginger, 1 part of ginger By weight, 2 parts by weight of pearl syrup and 3 parts by weight of peony. Spray amount is 70 g / min for the first minute, 50 g / min for 2 to 30 minutes, 3
It was set to 30 g / min from 1 minute to the end of the specified amount.
In addition, the blast flow was carried out at a temperature of 95 ° C.

After the spraying was completed, the granules were obtained by drying for 25 minutes while keeping the rolling motion. The apparent specific volume of the granulated product was 1.6 ml / g, and the particle size was as follows.

30 mesh residue: 4% 100 mesh residue: 95% 140 mesh residue: 1% 200 mesh residue: 0% 200 mesh passage: 0% Example 5 230 g of light anhydrous silicic acid was used in Example 1. Put it in a dynamic fluidized granulator and put a rotary disk at 300 rpm (peripheral speed 2.4 m /
It was rolled while rotating for 2 seconds. On the other hand, Bukyou 4
2000 g of water-extracted extract (moisture content: 2) obtained from 00 g, peony, keihi, toki and sojutsu (300 g), licorice and syrup (100 g), and senkyu (200 g).
0%, 400 g as a dry extract) was sprayed by a top spray at a spray rate of 40 g / min, and granulated while being tumbled and flowed at a blowing temperature of 70 ° C. After 50 minutes, it was dried for 30 minutes while being tumbled to obtain a granulated product. The apparent specific volume of the granulated product was 1.5 ml / g, and the particle size was as follows.

Remaining 30 mesh: 0% Retaining 100 mesh: 99% Retaining 140 mesh: 1% Retaining 200 mesh: 0% Passing through 200 mesh: 0% Example 6 As a rolling fluidized granulator, as shown in FIGS. The same breathable coating machine (Dower Coater, DRC500 manufactured by Paulec Co., Ltd.) similar to that shown was modified and used. That is, the breathable coating machine described above has a cross section 9 having nine inner walls.
It is provided with a rectangular rotary drum body, and punching metal is attached to each inner wall as a ventilation member. Instead of the nine ventilation members, every other two 150 mesh mesh nets were attached, and other inner walls were attached with non-breathable flat plates.

Anchusan 2492 g, corn starch 236 g, ECG 65 g, and light anhydrous silicic acid 1 used in Example 2
Put 42 g in a plastic bag and shake 10 times, put the mixture in the tumbling fluidized granulator, and rotate at 20 rpm.
Then, an air flow having a temperature of 80 ° C. was reversely supplied, and while being tumblingly flowed, the water extraction extract 3456 of Anchu-san in Example 2 was used.
g (23% concentration, 797.2 g as a dry extract) was sprayed for 3 hours at a spray rate of about 19 g / min.

After the spraying, the granules containing the powder and the extract were obtained by drying for 20 minutes while rolling and flowing. The apparent specific volume of the granulated product was 2.2 ml / g, and the particle size was as follows.

30 mesh residue: 5% 100 mesh residue: 71% 140 mesh residue: 10% 200 mesh residue: 7% 200 mesh passage: 7% Comparative Example Anchusan 623 g, corn starch 59 g, ECG16.
2 g and 35.5 g of light anhydrous silicic acid were put into a fluidized granulator (manufactured by Powrex Co., Ltd., FD-3S type). The composition ratio of 623 g of Anchusan is 3 parts by weight of Keihi powder,
3 parts by weight of Engosaku, 3 parts by weight of borei, 2 parts by weight of fennel, 2 parts by weight of licorice, and 2 ends of shukusha
By weight, 1 part by weight of Ryokyo powder.

Water was sprayed with a top spray at a spray rate of 45 ml / min for 9 minutes while flowing at a blast temperature of about 60 ° C., and then 864 g of the water extract of Annaka-san (23% concentration, 199.3 g of dry extract). ) Spray amount 96 g /
For 9 minutes, followed by water at a spray rate of 17 g / minute for 7 minutes.

After all the spraying was completed, the granules containing the powder and the extract were obtained by drying for 38 minutes while still flowing. The apparent specific volume of the granulated product was 2.7 ml / g, and the particle size was as follows, as compared with the granulated product obtained in Example 2,
It was bulky and had a broad particle size distribution.

30 mesh residue: 12% 100 mesh residue: 62% 140 mesh residue: 7% 200 mesh residue: 11% 200 mesh passage: 8% Experimental Example Of the granules obtained in Example 2 and Comparative Example, 30 to 10
5 g of 0 mesh granules were placed in a stainless steel cylinder (internal volume 50 ml, diameter 32 mmφ) and shaken for 5 minutes with a Specs mill (Specs company, Germany).
Then, it was passed through a 100-mesh round sieve and the amount on the sieve was measured to determine the residual ratio of the granulated product, which was defined as the strength of the granulated product.

As a result, the residual rate (strength) of the granulated product obtained in Example 2 was 82%, and the residual rate (strength) of the granulated product obtained in Comparative Example was 34%. The granulated product obtained in 1. exhibited twice or more the strength of the granulated product obtained in the comparative example.

[Brief description of drawings]

FIG. 1 is a longitudinal sectional view showing an example of a tumbling fluidized granulator.

FIG. 2 is a schematic view showing another example of a rolling fluidized granulator.

FIG. 3 is a schematic view showing still another example of the rolling fluidized granulator.

FIG. 4 is a schematic view showing another example of a rolling fluidized granulator.

FIG. 5 is a schematic vertical cross-sectional view showing still another example of the rolling fluidized granulator.

6 is a sectional view taken along line VI-VI of FIG.

[Explanation of symbols]

 1, 21, 31, 31, 41 ... Casing 6, 26, 36, 46 ... Rotating body 7, 27, 37, 47 ... Rotating body 14 ... Pipe 15 ... Nozzle 25 ... Vent hole 39 ... Slit 48 ... Vent member 51 ... Rotation Drum body 52 ... Ventilation member 53 ... Baffle plate 54 ... Spray nozzle

Claims (24)

[Claims] 1. A method for granulating a crude drug, which comprises rolling and flowing a crude drug component on the surface of a rotating body for granulation. 2. The method for granulating a crude drug according to claim 1, wherein the crude drug component and the additive are tumbled and flowed to granulate. 3. A crude drug according to claim 1, which is a method of granulating by spraying a liquid while rolling and flowing the granular material, wherein at least one of the granular material and the liquid contains a galenical component. Granulation method. 4. The method for granulating a crude drug according to claim 3, wherein the powdered crude drug or a powdery granule containing the powder and the additive is rolled and flowed. 5. Granulation by spraying a liquid containing at least one component selected from water, a herbal medicine extract and an additive while rolling and flowing the crude drug powder or a granular material containing the powder and the additive. Item 4. A method for granulating a crude drug according to Item 4. 6. The method for granulating a crude drug according to claim 4, wherein the total amount of the additives is 0.01 to 12 parts by weight with respect to 1 part by weight of the crude drug powder. 7. The method for granulating a crude drug according to claim 4, wherein the crude drug powder is a crude drug extract powder. 8. The method for granulating a crude drug according to claim 7, wherein the total amount of the additive is 0.01 to 100 parts by weight with respect to 1 part by weight of the crude drug extract powder. 9. The method for granulating a crude drug according to claim 3, wherein an aqueous or organic solvent liquid containing at least one component selected from a crude drug extract and an additive is sprayed. 10. While rolling and flowing the additive,
The method for granulating a crude drug according to claim 3, wherein a liquid containing at least a crude drug extract is sprayed for granulation. 11. The method for granulating a crude drug according to claim 10, wherein 0.01 to 20 parts by weight of the additive is used with respect to 1 part by weight of the crude drug extract in terms of dry extract. 12. The method for granulating a crude drug according to claim 10, wherein a liquid containing a crude drug extract and an additive is sprayed for granulation. 13. The method for granulating a crude drug according to claim 11, wherein a liquid containing 0.01 to 10 parts by weight of the additive is sprayed on 1 part by weight of the crude drug extract in terms of dry extract. 14. At least one component of an excipient, a binder and a disintegrant is used as an additive.
The method for granulating a crude drug according to any one of 1. 15. The method for granulating a crude drug according to claim 1, wherein a granulated product having an apparent specific volume of 0.5 to 2.5 ml / g is obtained. 16. The granulation of crude drug according to claim 1, wherein the crude drug component is tumbled on the surface of a rotating body provided at the bottom of the casing, and the rolled granular material is granulated by flowing by an air flow. Method. 17. The method of granulating a crude drug according to claim 16, wherein a rotating body having a central portion raised in a conical shape or a truncated cone shape is used. 18. A flow path between a bottom plate having an opening in the center and a rotating body rotatably disposed on the bottom plate,
The method for granulating a crude drug according to claim 16, wherein an air flow is introduced into the casing from the outer peripheral portion of the rotating body to cause the granular material rolling on the surface of the rotating body to flow. 19. The method for granulating herbal medicines according to claim 16, wherein stirring means is provided on the outer peripheral portion of the rotating body to carry out stirring rolling granulation. 20. The granulation of crude drug according to claim 1, wherein the crude drug component is tumbled along with the rotation of the rotary drum having a ventilation part on the inner wall, and is granulated by being caused to flow by the air flow from the ventilation part. Method. 21. The crude drug component is rhubarb, liquorice, cinnamon syrup, corydalis, borei, fennel, shukusha,
Ryokyo, Zio, Sanshuyu, Sanyaku, Takusha, Bukyou, Buttonpi, Processed Beetle, Carrot, Sojutsu, Koboku, Chinpi, Kobushi, Gyoza,
The method for granulating a herbal medicine according to claim 1, comprising at least one selected from taizo, peony, toki and senkyu. 22. Rolling and flowing the powdered crude drug containing the crude drug powder or the additive and the additive on the surface of the rotating body,
When granulating by spraying an aqueous liquid containing at least one component selected from crude drug extract and additives, at least 1 selected from excipients, binders and disintegrants per 1 part by weight of crude drug powder The method for granulating a crude drug according to claim 1, wherein a total amount of one additive is 0.01 to 12 parts by weight to obtain a granulated product having an apparent specific volume of 0.5 to 2.5 ml / g. 23. When granulating by spraying an aqueous liquid containing at least a crude drug extract while rolling and flowing the additive on the surface of a rotating body, to 1 part by weight of the crude drug extract in terms of dry extract. A granulated product having an apparent specific volume of 0.5 to 2.5 ml / g is obtained by using 0.01 to 20 parts by weight of at least one additive selected from the following: an excipient, a binder, and a disintegrant. A method for granulating the crude drug described. 24. A solid preparation containing the granulated product obtained by the method according to claim 1.