JP3296412B2 - Molded preparation and its manufacturing method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for continuously and rapidly molding a drug prescription component without causing any obstacle, and a molded preparation obtained by the method.

[0002]

2. Description of the Related Art In the production of pharmaceutical tablets, it is common technical knowledge to use a lubricant such as magnesium stearate in order to prevent tableting trouble, and in many cases, a lubricant is mixed with a drug prescription component. I'm tableting. However, when a large amount of lubricant is used, the disintegration time of the tablet, the dissolution rate becomes extremely slow,
In extreme cases, tablets may not disintegrate for hours.

[0003] For this reason, a method of forming a lubricant by adhering it to the compression molding machine side is considered. For example, Otsuka et al.
Abstracts of Annual Symposium on Preparation and Particle Design (1994)
Pp. 137) compared with tablets obtained by pre-coating magnesium stearate on the mortar and punch of the autograph and then compression-molding the drug prescription component to add a lubricant to the drug prescription component. A tablet having a high hardness and an extremely fast dissolution rate is obtained. However, this method
Since it is necessary to apply a lubricant to the mortar and punch of the autograph for each tablet, it cannot be an industrial production method.

Further, a method of injecting a lubricant powder into an upper punch / lower punch or an upper punch / lower punch and a die of a tableting machine, filling a drug prescription component in the die, and compression-molding the same (Japanese Patent Publication No. Sho 41) -1273,
JP-A-48-20103) is also known. In addition to the problem that this method sprays a lubricant that is fine particles, the lubricant scatters around the lubricant, that is, the nozzle, that is, a large device is required to collect the sprayed lubricant,
There is also a problem that the lubricant does not uniformly adhere to the punches and dies and a large amount of unnecessary lubricant remains near the lower punch, so that a large amount of lubricant is required.

Further, after the lubricant is compressed by a compression molding machine,
There is also known a method of compression-molding a processed material by using a lubricant remaining on a stamping wall (Japanese Patent Publication No. 47-31827). However, since this method is a technique for pelletizing ceramic, uranium oxide, or the like, there is a problem in applying it to the production of pharmaceuticals. That is, a lubricant such as an alkaline earth metal stearate commonly used in pharmaceutical tablets is poor in fluidity by itself, and it is difficult to stably supply it to a tableting machine. However, when these lubricants are tableted alone, a large amount of the lubricant adheres to the punch, and in severe cases, the lubricant adheres to the punch, which may hinder the subsequent tableting of drug components.

[0006]

SUMMARY OF THE INVENTION An object of the present invention is to improve the flowability of a lubricant and to efficiently produce a molded preparation.

[0007]

Means for Solving the Problems The present inventors have found that a lubricant alone has poor fluidity and it is difficult to supply only a lubricant to a tableting machine in continuous tableting. And when mixed with a lubricant, the fluidity is remarkably improved, and when the mixture is compressed, the lubricant is appropriately adhered to the surface of a punch and a die of a tableting machine; It has been found that, by tableting a drug prescription component with a machine, tableting can be performed without causing a tableting trouble without adding a lubricant to the prescription component.

Furthermore, it has been found that the tablets obtained by the present method have less disintegration and delay of dissolution due to the lubricant than tablets obtained by adding a lubricant to the drug formulation and tableting. Was.

That is, the present invention provides a molded preparation characterized by molding a mixture of a lubricant and a fluidizing agent by a molding machine, discharging the molded product, and then molding the drug prescription component by the molding machine. And a molded preparation obtained by the method.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The method of the present invention comprises molding a mixture of a lubricant and a fluidizing agent by a molding machine (hereinafter, primary molding).
After the molded product of the primary molding is discharged, the drug prescription component is molded by the molding machine (hereinafter, secondary molding). Lubricants used in the primary molding include stearic acid and palmitic acid. ,Magnesium stearate,
Higher fatty acids such as calcium stearate or alkaline earth metal salts thereof, soft silicic anhydride, synthetic aluminum silicate, hydrous silicon dioxide, silicon compounds such as talc, starches such as wheat starch, rice starch, corn starch, and sucrose fatty acids Esters and the like. Of these, alkaline earth metal stearate such as magnesium stearate and calcium stearate are preferred.

[0011] The fluidizing agent to be mixed with the lubricant is not particularly limited as long as it is a pharmaceutical additive usually used for oral administration and is a powder having excellent fluidity. The powder having excellent fluidity means, for example, a powder having an angle of repose of 60 ° or less, preferably 40 ° or less as measured by an injection method. It may be one obtained by pulverization or granulation, or a mixture thereof. From the viewpoint of miscibility with the lubricant, the particle size of the fluidizing agent is 5 to 2,000.
It is preferably in the range of μm, more preferably in the range of 50 to 750 μm. Further, when a compression molding method is used as the molding means, it is more preferable that the molding method is excellent.

Any formulation additive can be suitably used as a fluidizing agent as long as it satisfies the above conditions. However, if the formulation additive can be used as it is, operations such as pulverization and granulation can be performed. Is not particularly required. Such pharmaceutical additives include, for example, crystalline cellulose, lactose, sucrose, mannitol, calcium phosphate, calcium citrate, and the like, which are easily available, and have fluidity, compression moldability, and mixing with lubricants. And crystalline cellulose and lactose are most preferred.

[0013] Even if there are problems with fluidity, mixing with a lubricant and compression moldability as they are, they can be improved by pulverization or granulation.

The pulverization can be carried out by a conventional method using a jet mill, a hammer mill, a ball mill, a vibrating ball mill, a pin mill or the like.

Granulation is also performed by a known method, for example, wet granulation such as stirring granulation, extrusion granulation, fluidized bed granulation, and tumbling fluidized bed granulation, and dry compression granulation using a roller compactor or a roll granulator. It can be suitably implemented. When granulating, polyvinylpyrrolidone, hydroxypropyl methylcellulose,
A binder such as hydroxypropylcellulose and dextrin may be added.

In the primary molding, the ratio between the lubricant and the fluidizing agent varies depending on the molding method, the type of molding machine used for molding, the type of the lubricant and the fluidizing agent, the properties of the drug prescription components, and the like. Improve the flowability of the lubricant to improve the supply to the molding machine, make it easy to discharge the molded product after molding, and use the surface inside the molding machine after the molded product is discharged, such as a tableting machine. If there is no secondary molding on the surface of the mortar, punch, etc.,
The ratio is not particularly limited as long as the ratio allows the lubricant to adhere to such an extent that it can be efficiently molded.

The ratio can be easily determined by those skilled in the art by actually molding as appropriate and confirming the condition of the primary molded product, the secondary molded product and the molding machine.
For example, the amount of the fluidizing agent is preferably in the range of about 2 to 20 parts by weight, more preferably in the range of about 2 to 10 parts by weight with respect to 1 part by weight of the lubricant.

The primary molding using the above-mentioned components can be carried out by means and conditions usually used for molding a solid preparation. Examples of the molding means include a compression molding method such as tableting and roll compression, and a molding method that does not involve compression, such as mold molding. The method of the present invention is to leave the lubricant on the inner surface of the molding machine and to prevent the adhesion of the secondary molded product. .

In the case of compression molding, the compression pressure is such that the lubricant remains on the inner surface of the molding machine to the extent that the secondary molding can be prevented from adhering, and it is difficult to discharge the primary molding. It is sufficient if the pressure is in a range that does not exist. If the example of the pressure is described more specifically by taking a tableting machine as an example, for example, about 0.01 to 5000 kg / punch, preferably about 0.1
~ 4000kg / punch, more preferably about 1-3000k
g / punch, particularly preferably about 5-2000 kg / punch, with about 10-1000 kg / punch being most preferred.

Although the term "primary molding" is used in the method of the present invention, the primary molded product does not necessarily have to maintain a clear shape after being discharged. As long as the lubricant remains on the surface as described above so as to be easily formed into a secondary form, the lubricant includes any one that collapses upon discharge.

The molded product thus formed is discharged and subjected to secondary molding. The secondary molding can be easily carried out by ordinary molding means and conditions. However, in the method of the present invention, as described above, since the lubricant remains on the inner surface of the molding machine due to the primary molding. No need to use lubricants. Further, according to the method of the present invention, even a drug prescription component containing a lubricant can be molded more efficiently, so that there is no problem at all.

In the secondary molding, a drug formulation comprising a target drug and various pharmaceutical additives (excipients, binders, disintegrants, etc.) is supplied to a molding machine and, as in the primary molding, a solid preparation is prepared. It can be carried out by the means and conditions used in molding.

The drug is not particularly limited as long as it can be administered orally. For example, chemotherapeutics, antibiotics, respiratory stimulants, antitussives, anticancer drugs, drugs for autonomic nerves, drugs for psychiatric nerves, local anesthetics, muscle relaxants, drugs for digestive organs, antihistamines, drugs for poisoning , Sedative, hypnotic, antiepileptic, antipyretic analgesic and anti-inflammatory, inotropic, antiarrhythmic,
Examples include various drugs such as diuretics, vasodilators, antilipidemic agents, nutrient tonics, anticoagulants, drugs for the liver, hypoglycemic agents, hypotensive agents and the like.

There are no particular restrictions on the pharmaceutical additives, and all additives that can be used as solid pharmaceuticals can be suitably used. Such additives include, for example, lactose, sucrose, mannitol, xylitol, erythritol, sorbitol, maltitol, calcium citrate, calcium phosphate, excipients such as crystalline cellulose, corn starch, potato starch, sodium carboxymethyl starch, partially pregelatinized. Starch, carboxymethylcellulose calcium, carboxymethylcellulose,
Disintegrants such as low-substituted hydroxypropylcellulose and crosslinked sodium carboxymethylcellulose, binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyethylene glycol, dextrin, pregelatinized starch, magnesium stearate, calcium stearate, talc, light Lubricants such as silicic anhydride, hydrous silicon dioxide, and further phospholipids, glycerin fatty acid esters,
Surfactants such as sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, sucrose fatty acid ester, or flavors such as orange and strawberry, iron sesquioxide, Yellow iron sesquioxide, Food Yellow No. 5, Food Yellow No. 4,
Coloring agents such as aluminum chelates, sweeteners such as saccharin and aspartame, flavoring agents such as citric acid, sodium citrate, succinic acid, tartaric acid, fumaric acid, and glutamic acid, dissolution aids such as cyclodextrin, arginine, lysine, and trisaminomethane The agent is raised.

The lubricant can be selected from various states depending on the purpose of the preparation, from a state in which the lubricant is not blended at all to a state in which an appropriate amount is blended.

Granulation granules may be contained in the drug formulation component to be supplied, and the granulation may be performed by a known method, for example, stirring granulation, extrusion granulation, fluidized bed granulation, tumbling fluidized bed granulation. In addition to wet granulation, such as layering granulation to coat the drug on an inert carrier such as sucrose, crystalline cellulose, heat-melt granulation using wax that melts by heating, dry compression granulation, etc. It can be suitably implemented.

Further, the drug prescription component at the time of molding may be in a state not containing water or various solvents, or may be in a state containing it.

The molding means may be the same as the primary molding.

When the molding means is compression molding, the compression pressure will be described more specifically by taking a tableting machine as an example. For example, about 0.01 to 5000 kg / punch, preferably about 0.1 to 4000 kg / punch , More preferably about 1-3
000 kg / punch, particularly preferably about 5 to 2000 k
g / punch, with about 10-1000 kg / punch being most preferred.

In the method of the present invention, it is most effective to alternately perform primary and secondary molding alternately. Therefore, when a tableting machine is used, a multi-layer tableting machine is used rather than an ordinary tableting machine. (Laminated tableting machine of Hata Iron Works, three-layer rotary tablet machine of Kikusui Seisakusho) and double tablet machine (double tableting machine of Hata Iron Works, double super high pressure rotary powder molding machine of Kikusui Seisakusho), etc. It is more efficient to use.

When a double tablet machine is used, a mixture of a lubricant and a fluidizing agent is supplied to one compression section (hereinafter, referred to as compression section A), and the other compression section (hereinafter, compression section A). B) is supplied with the drug prescription component. The mixture of the lubricant and the fluidizing agent supplied to the compression site A is compression-molded (primary molding), and at this time, the lubricant adheres to the surfaces of the mill and the punch. The primary molded product is immediately discharged and collected. Subsequently, the drug prescription component is supplied into the die to which the lubricant has adhered, and compression-molded at the compression site B (secondary molding). The secondary molded product, that is, the target tablet is immediately discharged and collected. Then, the mixture of the lubricant and the fluidizing agent is supplied to the compression portion A again, and the above cycle is repeated.

When a three-layer tablet machine is used as a multilayer tablet machine, lubricating is performed in one of two pre-compression sites out of two compression sites, ie, two pre-compression sites and one main compression site. The operation may be performed by supplying a mixture of the agent and the fluidizing agent, and supplying the drug prescription component to the main compression site. For example, a case where a mixture of a lubricant and a fluidizing agent is supplied to the first pre-compression section, nothing is supplied to the second pre-compression section, and the drug prescription component is supplied to the main compression section is as follows. Will be described. The mixture of the lubricant and the fluidizing agent supplied to the first preliminary compression section is compression molded (primary molding), and at this time, the lubricant adheres to the surfaces of the mortar and the punch. The primary molded product is immediately discharged and collected. Nothing is supplied in the subsequent second pre-compression section, and the drug prescription component is supplied in the main compression section and compression-molded (secondary molding). The secondary molded product, that is, the target tablet is immediately discharged and collected. Then, the mixture of the lubricant and the fluidizing agent is supplied to the first pre-compression portion again, and the above cycle is repeated.

With the above apparatus, a mixture of a lubricant and a fluidizing agent and a drug prescription component are alternately tableted with the same punch and die. The prescription component is tableted, and continuous tableting is possible without causing a tableting trouble without adding a lubricant to the prescription component.

The recovered primary molded product, that is, the compression molded product of the mixture of the lubricant and the fluidizing agent may be discarded as it is, but it is more economically preferable to grind and reuse it.

The drug-containing tablet obtained according to the present invention can be orally administered as it is as an uncoated tablet, but it may be coated with sugar coating, film coating, compression coating or the like, if necessary. Can be implemented.

Further, the method of the present invention can be applied to the production of any pharmaceutical preparation as long as it includes a molding step. Very effective. That is,
Such a rapidly disintegrating preparation in the oral cavity needs to be dissolved in the mouth in a very short time, so that it is difficult to mix a lubricant into the prescription component, but according to the method of the present invention, the lubricant is molded. Because a thin lubricant layer is formed only on the surface of the solid preparation,
It does not hinder continuous molding and has no effect on the dissolution rate.

[0037] Such a rapidly disintegrating preparation in the oral cavity includes:
(A) a preparation obtained by a method of molding and then humidifying and drying a drug prescription component, or (b) a preparation obtained by a method of molding and drying a moderately moistened drug prescription component, Any of them can be suitably combined with the present invention.

The method (a) will be specifically described. A mixture of a lubricant and a fluidizing agent is supplied to a molding machine to perform primary molding, and the molded product is discharged. Subsequently, the drug prescription component is supplied to a molding machine, which is secondarily molded to a low density, and then the molded article is maintained under humidification and dried to obtain a rapidly disintegrating oral preparation.

As the drug prescription component, it is preferable to use a mixture of a drug and a substance which is moisturized by humidification so as to be moldable and which maintains its shape by drying after humidification (hereinafter, simply referred to as a wet substance). Such a mixture may be granulated by an ordinary method, if necessary.

Examples of the wetting substance include saccharides, sugar alcohols and water-soluble high-molecular substances having such properties.
Examples of sugars include monosaccharides and oligosaccharides such as glucose, fructose, lactose, and sucrose.Examples of sugar alcohols include mannitol, sorbitol, maltitol, erythritol, xylitol, and the like. Examples include hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, dextrin, hydroxyethylcellulose, polyethylene glycol and the like. Of these, glucose, sucrose, mannitol, xylitol, dextrin, polyvinylpyrrolidone and polyethylene glycol are particularly preferred.

These substances are not particularly limited, as long as they are of a grade generally used in the field of pharmaceuticals. These wetting substances can be used alone or as a mixture at an arbitrary ratio.

Of course, these moist substances have different levels of hygroscopicity, for example, glucose,
Fructose, sucrose, xylitol, sorbitol, maltitol, dextrin, polyvinylpyrrolidone, hydroxyethylcellulose, polyethylene glycol and the like are strong, and mannitol, erythritol and the like are relatively weak, so that a suitable formulation can be obtained by appropriately combining these. .

For example, by increasing the amount of a substance having a high hygroscopicity, it is possible to obtain a preparation having excellent moldability and strong, and by increasing the substance having a low hygroscopicity, it is possible to obtain a preparation which rapidly disintegrates.

When a plurality of wettable substances are used in combination, a relatively preferable combination is, for example, a combination of a monosaccharide or oligosaccharide such as glucose, fructose or sucrose with a sugar alcohol such as mannitol, sorbitol or erythritol. Examples include a combination of a saccharide or oligosaccharide with a water-soluble polymer such as polyvinylpyrrolidone, hydroxyethyl cellulose, and polyethylene glycol, and a combination of a sugar alcohol and a water-soluble polymer.

Further, a more preferable combination is, for example, mannitol / sucrose, erythritol /
Examples include glucose, mannitol / maltitol, xylitol / polyvinylpyrrolidone, mannitol / polyvinylpyrrolidone, erythritol / sucrose, xylitol / polyvinylpyrrolidone, and the like. These are not limited to two components, and any components can be blended and used. For example, if a combination of three components is used, preferred examples include mannitol, erythritol and sucrose, mannitol, erythritol and polyvinylpyrrolidone. In particular, many monosaccharides, oligosaccharides, and sugar alcohols have similar behaviors to water, and if they belong to the same category, the composition can be easily changed or added.

In addition to the above-mentioned components, ie, a drug and a wetting substance, additives commonly used in the field of formulation technology can be added.

Examples of such additives include the above-mentioned excipients, binders, disintegrants, lubricants, surfactants, flavors, coloring agents, sweeteners, corrigents, and solubilizers.

Any of these components can be used alone or in an appropriate mixture as appropriate as long as the disintegration and moldability of the orally rapidly disintegrating preparation are not impaired. For example, lactose / sucrose / Examples include magnesium stearate, mannitol / corn starch / polyvinylpyrrolidone / orange flavor.

The mixing ratio of the drug and the wetting substance is not particularly limited, but considering the solubility of the drug in water, the amount of the drug is about 0.000 per part by weight of the wetting substance.
It is sufficient if it is contained in an amount of from about 0.1 to about 3 parts by weight, and especially about 0.
Preferably, it is present in an amount of from 0001 to about 1 part by weight.

The molding can be carried out by the molding method of the present invention so that the molded article has a desired shape while maintaining a low density. Specifically, a mixture of a lubricant and a fluidizing agent is supplied to a molding machine to perform primary molding, and after the molded product is discharged, a mixture obtained by mixing a drug, a wet substance, and other formulation additives is molded. , And then subjected to secondary molding. When the compression molding method is used as the molding means, for example, about 1000 k
g / punch or less, preferably about 0.01 kg to 500 kg /
The pressure can be appropriately selected in the range of a punch or the like, and the pressure can be determined in consideration of the molding maintaining power and disintegration of the compounded drug and the wet substance while maintaining the density in a desired range. .

The rapidly disintegrating preparation in the oral cavity obtained by this production method can be formed into a low density, then humidified and dried to obtain a large pore and high disintegration in the mouth.
This is important. The specific density is about 0.4 to about 1.3 g / cm ³ , and there is no inconvenience in this range.

The humidification condition is not particularly limited as long as it is a condition that is equal to or higher than the normal humidity. The humidification condition is such that the molded product of the mixture of the drug and the moist substance is moist and moist as a whole, or Any condition may be used as long as some or all of the wet substance absorbs moisture and becomes moist. Further, the condition may be such that a part or a specific component of the wet substance deliquesces. In short, it is only necessary to set conditions so that the hardness of the molded product after humidification and drying is higher than that before humidification.From the viewpoint of workability, the higher the humidity, the shorter the required time. The optimum relative humidity may be appropriately selected at a value equal to or higher than the critical relative humidity of the mixture calculated by the hypothesis [edited by Ichigase, New Pharmaceutical Science (Hirokawa Shoten), published on September 10, 1993, page 96].

The humidification may be performed at elevated temperature or at ordinary temperature, and is not particularly limited. The temperature may be set in consideration of the effects of the compounded drug and the wet substance on the temperature. Further, the humidifying means is not particularly limited, and a known means, for example, a humidifier such as a spray-type humidifier, a warming-type humidifier (for example, a constant temperature / humidifier, manufactured by Tabai Espec Corporation) may be used. I just need.

The optimum humidification conditions vary depending on the apparent critical relative humidity of the mixture. To illustrate the humidification conditions, in the case of mannitol / sucrose, for example, a humidity of about 70 to
100 RH%, more preferably about 80 to 100 RH%,
Particularly preferably, it is about 90 to 100 RH%,
The temperature is from about 10 to about 70C, more preferably from about 15 to about 5
Conditions such as 0 ° C., particularly preferably from about 20 to about 30 ° C. are mentioned.

The drying is carried out to increase the hardness of the preparation after humidification and to remove moisture, and can be carried out at normal temperature to warming and normal pressure to reduced pressure under appropriate conditions.

In the present production method, the particle size of the drug and the additive is not particularly limited, but the smaller the particle size, the better the feeling of taking.

When the discomfort such as bitterness and smell of the drug is strong, the drug can be used after being processed with a coating agent, a flavoring agent, or a flavoring agent capable of concealing them.
If these coating agents and flavoring agents, flavoring agents and processing methods are used in the ordinary technical field,
It can be used without any restrictions.

The present preparation can be formed into any shape, for example, into various shapes such as a tablet, an ellipse, a sphere and a square. Furthermore, it can be molded into a certain shape, humidified, dried and then pulverized to obtain granules, fine granules and powder.

The porosity of the preparation is, for example, about 10 to 70.
%, More preferably from about 15 to about 65%, particularly preferably from about 20 to about 50%.

As a modification of the above method (a), a similar rapidly disintegrating preparation in the oral cavity can be obtained by molding a drug prescription component, moistening it with alcohol, and removing the alcohol. . Specifically, a mixture of a lubricant and a fluidizing agent is supplied to a molding machine to perform primary molding, and the molded product is discharged. Subsequently, the drug prescription component is supplied to a molding machine, and after low-density secondary molding, the molded product is wetted with alcohol to remove the alcohol.

In the present method, examples of the alcohol include lower alcohols such as methanol, ethanol and isopropanol, and among them, ethanol is preferred.

It is preferable to use a mixture of the drug and the above-mentioned alcohol-soluble binder (alcohol-soluble binder) as the drug formulation component.
If necessary, granulation may be performed by a conventional method.

Examples of the alcohol-soluble binder include polyvinylpyrrolidone, hydroxypropylcellulose, ethylcellulose and the like, with polyvinylpyrrolidone being preferred.

In addition to the above-mentioned components, that is, the drug and the alcohol-soluble binder, additives commonly used in the field of formulation technology can be added. Examples of such additives include the above-mentioned excipients, binders, disintegrants, lubricants, surfactants, fragrances, coloring agents, sweeteners, corrigents, and solubilizers. Sugars and sugar alcohols in the method are particularly preferred. These components are in a range that does not impair the disintegration and moldability of the rapidly disintegrating oral preparation,
Any appropriate amount can be used alone or as a mixture.

The blending amount of the alcohol-soluble binder is not particularly limited and can be appropriately determined according to the desired disintegration and hardness of the preparation.
It is 1 to 30% by weight, preferably about 1 to 10% by weight.

In the preparation obtained by this method, the density after molding is important as in the method (a), and when this density is specifically exemplified, about 0.4 to about 1.3 g / cm ³ is appropriate. It is.

As in the case of the method (a), the molding may be carried out by the molding method of the present invention so as to obtain a desired shape while maintaining a low density.

The method of wetting with alcohol is not particularly limited, but some or all of the alcohol-soluble water-soluble binder in the molded product is moist, and the hardness of the preparation after alcohol removal is higher than that before alcohol wetting. Conditions are acceptable. For example, there are methods such as maintaining the molded product in the presence of alcohol vapor, spraying the molded product with alcohol, and pouring alcohol into the molded product.

When the molded product is maintained in the presence of alcohol vapor, the molded product may be stored in a desiccator or the like filled with alcohol vapor for a certain period of time. The storage time is
It can be appropriately determined according to the disintegration and hardness of the preparation, and in general, the longer the storage time, the higher the preparation having a higher hardness.

When spraying alcohol on a molded product,
What is necessary is just to perform using the spraying apparatus generally used in the formulation machine, such as a spray gun. The spray amount can be determined according to the disintegration and hardness of the target preparation within a range that does not cause the molded product to collapse.

When pouring alcohol into a molded product,
What is necessary is just to perform using the fixed-quantity supply apparatus generally used.
The amount to be added can be determined according to the disintegration property and hardness of the target preparation within a range that does not cause the molded product to collapse.

The alcohol may be removed from the molded product by evaporating the alcohol. Similar to the drying in the method (a), the alcohol is removed under normal temperature to heating and normal pressure to reduced pressure under appropriate conditions. be able to.

Next, the method (b) will be specifically described. A mixture of a lubricant and a fluidizing agent is supplied to a molding machine to perform primary molding, and after the molded product is discharged, a wet drug formulation is prepared. It can be manufactured by supplying the components to a molding machine, performing secondary molding, and then drying the molded product.

It is preferable that the drug prescription component in a wet state is a mixture containing a drug, a saccharide, and water enough to wet the particle surface of the saccharide.

As the saccharide, any saccharide can be used as long as it is water-soluble and does not adversely affect the drug (for example, decomposition of the drug). For example, monosaccharides such as sucrose, glucose, maltose, fructose, and lactose can be used. Or oligosaccharides, sorbitol, mannitol, maltitol, xylitol,
A sugar alcohol such as erythritol is used.
These saccharides may be used alone or in combination of two or more.

Preferred sugars include, for example, sucrose,
Glucose, maltitol, xylitol, erythritol and the like.

The average particle size of the saccharide is usually from 1 to 100.
μm, preferably 10 to 80 μm, more preferably 40 μm.
〜60 μm.

The content of the saccharide in the drug prescription component varies depending on the kind of the drug, but is usually about 5 to 95% by weight, preferably about 10 to 90% by weight, and more preferably about 20 to 80% by weight.

For example, when a small dose of a drug is used and the drug content in the drug formulation is 0.1 to 10% by weight, the saccharide content is usually 20 to 90% by weight, preferably Is 30 to 90% by weight, more preferably 50 to 9% by weight.
It is about 0% by weight.

When a moderate amount of drug is used and the drug content in the drug formulation is 10 to 30% by weight, the saccharide content is usually 20 to 90% by weight, preferably Is 30 to 80% by weight, more preferably 50 to 80% by weight.
% By weight.

Further, when a drug with a large dose is used and the content of the drug in the drug formulation is 30 to 70% by weight, the saccharide content is usually 10 to 70% by weight, preferably 20 to 70% by weight. About 60% by weight, more preferably about 30 to 50% by weight.

[0082] The drug formulation components may contain various pharmaceutical additives generally used for the production of pharmaceuticals, as long as the effects of the present method are not hindered.

Examples of such additives include the above-mentioned excipients, binders, disintegrants, lubricants, surfactants, flavors, coloring agents, sweeteners, corrigents, and solubilizers.

These additives may be used alone or in combination of two or more.
For example, an appropriate amount can be appropriately added at the time of mixing of the drug and the saccharide, at the time of adding water, at the time of kneading, or before and after these steps.

The amount of water in the drug prescription component may be such that the surface of the saccharide particles contained in the drug prescription component gets wet. In the present method, since water is added to the extent that the surface of the saccharide particles is moistened, when molded and dried, the saccharide particles are fused together, and a porous material having an appropriate porosity and hardness as a rapidly disintegrating preparation in the oral cavity. A molded preparation is obtained.

The amount of water to be added varies depending on the types and amounts of drugs, sugars and additives, but is usually 0.1 to 10% by weight, preferably 0.3 to 10% by weight, in the drug formulation components. Preferably 0.5 to 8% by weight, more preferably 0.5 to 5% by weight, most preferably about 1 to 5% by weight is added. When the amount of water added is small, the strength of the preparation decreases, and when it is large, the medicinal component and the like easily adhere to a molding machine (for example, a punch, a die, etc.) at the time of molding, and production becomes difficult.

More specifically, for example, when 20 to 40% by weight of xylitol and / or maltitol is contained as a saccharide in a drug component, the water content is usually 1 to 5% by weight, preferably 2 to 3% by weight. % May be added.
In addition, sucrose and / or glucose are used as sugars for 60 to
In the case of containing 80% by weight, it is usually sufficient that 2 to 4% by weight of water is added. Further, when erythritol is contained as a saccharide in an amount of 55 to 75% by weight, it is usually sufficient that water is added in an amount of 1 to 3% by weight.

The method of adding water is not particularly limited, and may be added all at once, or may be added dropwise or sprayed.

The mixing of the drug with the saccharide and the like is carried out by a mixing method generally used in the production of pharmaceuticals, for example, mixing, kneading, sieving and the like. Specifically, mixing can be performed using a double cone mixer, a fluidized bed granulator, a high-speed stirring granulator, a vibration sieve, or the like.

The mixture containing the drug, saccharide and water is kneaded before molding. For kneading the mixture containing water, a method generally used as a means for producing a preparation can be used. For example, kneading can be carried out using the above-described device used when mixing a medicinal ingredient and a saccharide or the like.

The molding can be performed by the molding method of the present invention. Specifically, a mixture of a lubricant and a fluidizing agent is supplied to a molding machine to perform primary molding, and after the molded product is discharged, The wet prescription component may be supplied to a molding machine to perform secondary molding. When the compression molding method is used as the molding means, 2 to 130 kg / punch, preferably 4 to 100 kg / punch
It may be compressed with a punch, more preferably about 6 to 40 kg / punch. The temperature at the time of molding is such that the saccharide particles do not dissolve or melt, and is usually room temperature (for example, about 20 to 30 ° C), and preferably about 25 ° C.

It is preferable to further dry the molded product obtained as described above. Drying is, for example, vacuum drying,
It can be carried out by any method generally used in the production of preparations, such as freeze-drying and natural drying.

These molded preparations may be further coated by a coating method generally used in the production of coated preparations to such an extent that the strength and solubility of the preparations are not adversely affected.

The orally rapidly disintegrating preparation thus obtained is
It has a porous structure. The porous structure here means
It usually means that the porosity is 10 to 70%, preferably 15 to 60%. Therefore, the tablet of the present invention is excellent in disintegration and solubility in the oral cavity, and also has high drop strength.

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

[0096]

【Example】

Experimental Example 1 193 parts by weight of mannitol and 5 parts by weight of imidapril hydrochloride were mixed and granulated by spraying 2 parts by weight of polyvinylpyrrolidone with a 5% (w / w) aqueous solution in a fluidized bed granulator under flow. The obtained granules were used as drug formulation components. Further, magnesium stearate was used as a lubricant, and crystalline cellulose (Avicel PH102: manufactured by Asahi Kasei) was used as a fluidizing agent.
The mixture was mixed at a ratio of 9, 19 parts by weight to prepare four types of mixtures having different mixing ratios. Using a three-layer tablet machine (manufactured by Kikusui Seisakusho, punch size: diameter 10 mm), a mixture of a lubricant and a fluidizing agent was supplied to the first pre-compression portion (primary molding), and the second
Nothing was supplied to the pre-compressed part, and the drug prescription component was supplied (secondary molding) to the main compressed part and continuous tableting was performed. The primary molded product is tableted to 200 mg / tablet and the hardness is 1 kg.
The secondary molded product was tableted so as to have a hardness of 300 mg / tablet and a hardness of 9 kg.

In the case of continuous tableting using any mixture having a different mixing ratio between the lubricant and the fluidizing agent in the primary molding,
100 tablets were produced from the secondary molded product, and no tableting trouble occurred.

Experimental Example 2 73 parts by weight of trimebutine maleate, 2 parts by weight of hydroxypropylmethylcellulose (TC-5, manufactured by Shin-Etsu Chemical Co., Ltd.) and 25 parts by weight of crystalline cellulose were mixed and used as a drug formulation component. In addition, magnesium stearate is used as a lubricant, and crystalline cellulose (Avicel PH) is used as a fluidizing agent.
102: manufactured by Asahi Kasei Co., Ltd.), and a fluidizing agent was mixed at a ratio of 4.9 parts by weight with respect to 1 part by weight of a lubricant to prepare two kinds of mixtures having different mixing ratios. As in Experimental Example 1, a mixture of a lubricant and a fluidizing agent and a drug formulation component were continuously tableted using a three-layer tablet machine. 200 mg / tablet for the primary molded product, tableting with hardness of 1 kg, 250 mg / tablet for the secondary molded product
Tablets and tablets were pressed to a hardness of 11 kg.

In the case of continuous tableting using any mixture having a different mixing ratio between the lubricant and the fluidizing agent in the primary molding,
100 tablets were produced from the secondary molded product, and no tableting trouble occurred.

Experimental Example 3 Magnesium stearate was used as a lubricant, and crystalline cellulose (Avicel PH102: manufactured by Asahi Kasei), β-anhydrolactose or granulated lactose (lactose G: manufactured by Freund Corporation) was used as a fluidizing agent. Fluidizing agent 9 per 1 part by weight of powder
Parts by weight were mixed to prepare three types of mixtures each having a different type of fluidizing agent. As a drug prescription component, the one prepared in Experimental Example 2 was used, and a mixture of a lubricant and a fluidizing agent and a drug prescription component were continuously tableted using a three-layer tableting machine in the same manner as in Experimental Example 1. 200 mg / tablet for the primary molded product, tableting with hardness of 1 kg, 250 mg / tablet for the secondary molded product
Tablets and tablets were pressed to a hardness of 11 kg.

Even when any mixture of different types of fluidizing agents was used, tableting could be performed without any tableting trouble during continuous tableting.

Example 1 After mixing 5 parts by weight of imidapril hydrochloride, 75 parts by weight of lactose and 20 parts by weight of polyethylene glycol (molecular weight: 6000), the mixture was granulated by heating at 80 ° C. in an external bath at a high speed mixer (Fukae Kogyo). A drug formulation was prepared. Also,
15 parts by weight of magnesium stearate as a lubricant and granulated lactose (lactose G: manufactured by Freund Corporation) as a fluidizing agent 8
5 parts by weight were mixed to prepare a mixture of a lubricant and a fluidizing agent. Three-layer tablet machine (Kikusui Seisakusho, punch size: 7m in diameter)
m), the mixture of the lubricant and the fluidizing agent is supplied to the first precompression section (primary molding), nothing is supplied to the second precompression section, and the drug prescription is supplied to the main compression section. The components were supplied (secondary molding) and continuously tableted. 100 mg /
Tablets, tableted to a hardness of 1 kg, secondary molding 10
Tablets were pressed so that the hardness was 0 mg / tablet and the hardness was 4 kg. Even during continuous tableting, tableting could be performed without any tableting trouble.

Example 2 A mixture of a drug formulation component, a lubricant and a fluidizing agent prepared in Example 1 was mixed with a compound tablet machine (manufactured by Hata Iron Works, punch size: diameter 7
mm). A mixture of a lubricant and a fluidizing agent was supplied to one compression site, and a drug prescription component was supplied to the other compression site, and continuous tableting was performed. The primary molded product is 100
mg / tablet and hardness were 1 kg, and the secondary molded product was 100 mg / tablet and hardness was 4 kg.
Even during continuous tableting, tableting could be performed without any tableting trouble.

Example 3 175 parts by weight of mannitol and 5 parts by weight of imidapril hydrochloride were mixed, and granulated by spraying 20 parts by weight of sucrose with a 30% (w / w) aqueous solution under fluidization in a fluidized bed granulator. The obtained granules were used as drug formulation components. Further, 20 parts by weight of calcium stearate as a lubricant and 80 parts by weight of mannitol as a fluidizing agent were mixed to prepare a mixture of the lubricant and the fluidizing agent. In addition, what carried out dry compression granulation with the roller compactor and the roll granulator was used for mannitol as a fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. 200mg / tablet for primary molding,
The tablet is pressed to a hardness of 2 kg, and the secondary molded product is 200 m
g / tablet, and tableted to a hardness of 5 kg. Even during continuous tableting, tableting could be performed without any tableting trouble.

Example 4 Naproxen 100 parts by weight, corn starch 1
2.5 parts by weight were mixed, 6 parts by weight of polyvinylpyrrolidone was added as an 8% (w / w) solution (50% ethanol solution), and the mixture was stirred and granulated using a Shinagawa mixer to obtain granulated granules. Was added with 6.5 parts by weight of carboxymethylcellulose calcium to give a drug formulation component. Also, 20 parts by weight of magnesium stearate as a lubricant, 5 parts by weight of hydrous silicon dioxide and 75 parts by weight of sucrose as a fluidizing agent were mixed to prepare a mixture of the lubricant and the fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. 150m for primary molding
g / tablet and hardness were 3 kg, and the secondary molded product was 125 mg / tablet and hardness was 5 kg. Even during continuous tableting, tableting could be performed without any tableting trouble.

Example 5 5 parts by weight of bisoprolol fumarate and 87 parts by weight of mannitol were mixed, and 8 parts by weight of polyethylene glycol was added to 10 parts by weight.
% (W / w) solution (50% ethanol solution), and the mixture was stirred and granulated using a Shinagawa mixer, and the obtained granulated granules were used as drug formulation components. Also, 10 parts by weight of magnesium stearate as a lubricant, 5 parts by weight of stearic acid, and 85 parts by weight of calcium phosphate as a fluidizing agent were mixed to prepare a mixture of a lubricant and a fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. 150mg /
Tablets, tableted to a hardness of 4 kg, secondary molded product 10
Tablets were pressed so that the hardness was 0 mg / tablet and the hardness was 4 kg. Even during continuous tableting, tableting could be performed without any tableting trouble.

Example 6 5 parts by weight of imidapril hydrochloride and 68 parts by weight of lactose were mixed.
In a fluidized bed granulator, 7 parts by weight of polyethylene glycol (molecular weight: 6000) was fluidized in a 20% (w / w) solution (50%).
% Ethanol solution) and granulated, and the obtained granules were used as drug formulation components. Also, 5 parts by weight of calcium stearate, 5 parts by weight of synthetic aluminum silicate and 90 parts by weight of calcium citrate as a fluidizing agent were mixed to prepare a mixture of a lubricant and a fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. The primary molded product was tableted at 150 mg / tablet and hardness of 2 kg, and the secondary molded product was tableted at 80 mg / tablet and hardness of 3.5 kg. Even during continuous tableting, tableting could be performed without any tableting trouble.

Example 7 189 parts by weight of mannitol and 5 parts by weight of imidapril hydrochloride were mixed, and granulated by spraying 6 parts by weight of polyvinylpyrrolidone with a 10% (w / w) aqueous solution in a fluidized bed granulator under flow. Then, the obtained granules were used as drug formulation components. Also, 10 parts by weight of calcium stearate as a lubricant and 90 parts by weight of β-anhydrolactose as a fluidizing agent were mixed to prepare a mixture of the lubricant and the fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. 200mg / tablet for primary molding,
The tablet is pressed to a hardness of 1 kg, and the secondary molded product is 200 m
g / tablet, and tableting was performed so that the hardness became 0.5 kg. Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was left in a desiccator filled with ethanol vapor at 25 ° C. for 5 hours, and then placed in a box dryer (40 ° C.) for 3 hours.
The ethanol was removed by holding for a period of time to obtain a rapidly disintegrating tablet in the oral cavity.

Example 8 25 parts by weight of magnesium stearate as a lubricant and granulated lactose (lactose G: manufactured by Freund Corporation) 7 as a fluidizing agent
5 parts by weight were mixed to prepare a mixture of a lubricant and a fluidizing agent. The mixture of the lubricant and the fluidizing agent, and the drug prescription component prepared in Example 7 were continuously tableted using a three-layer tablet machine in the same manner as in Example 1. 180 mg / tablet for primary molded product, tableting with hardness of 1 kg, 200 mg for secondary molded product
/ Tablet, tableted to a hardness of 1 kg. Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was allowed to stand at 25 ° C. and 90% RH for 5 hours, and then dried in a box dryer (45 ° C.) for 5 hours to obtain a rapidly disintegrating tablet in the oral cavity. Was.

Example 9 189 parts by weight of mannitol, bisoprolol fumarate 5
Parts by weight, and 6 parts by weight of polyvinylpyrrolidone was sprayed with a 10% (w / w) aqueous solution under a fluidized bed in a fluidized bed granulator to granulate, and the obtained granules were used as drug formulation components. . Also, 10 parts by weight of calcium stearate as a lubricant and 90 parts by weight of β-anhydrolactose as a fluidizing agent were mixed to prepare a mixture of the lubricant and the fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug formulation components were continuously tableted using a three-layer tableting machine. 200mg for primary molding
/ Tablet, tablet hardness was 1.5 kg, and the secondary molded product was 200 mg / tablet, tablet hardness was 1 kg.
Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was left in a desiccator filled with ethanol vapor at 25 ° C. for 5 hours, and then placed in a box dryer (40
° C) for 3 hours to remove ethanol to obtain a rapidly disintegrating tablet in the oral cavity.

Example 10 25 parts by weight of magnesium stearate as a lubricant and granulated lactose (lactose G: manufactured by Freund Corporation) 7 as a fluidizing agent
5 parts by weight were mixed to prepare a mixture of a lubricant and a fluidizing agent. The mixture of the lubricant and the fluidizing agent, and the drug prescription component prepared in Example 9 were continuously tableted using a three-layer tableting machine in the same manner as in Example 1. 180 mg / tablet for primary molded product, tableting with hardness of 2 kg, 200 mg for secondary molded product
/ Tablets were pressed so that the hardness became 1 kg. Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was left at 25 ° C. and 90% RH for 5 hours,
It was kept in a box dryer (45 ° C.) for 5 hours and dried to obtain a rapidly disintegrating tablet in the oral cavity.

Example 11 160 parts by weight of mannitol, (1-methyl-L-4,5
-Dihydroorotyl) -L-histidyl-L-prolinamide 5 parts by weight, and granulation by spraying 40 parts by weight of sucrose with a 30% (w / w) aqueous solution under flow in a fluidized bed granulator. Then, the obtained granules were used as drug formulation components. 10 parts by weight of magnesium stearate and 10 parts by weight of calcium stearate as a lubricant were mixed with 80 parts by weight of crystalline cellulose (Avicel PH102: manufactured by Asahi Kasei) as a fluidizing agent to prepare a mixture of the lubricant and the fluidizing agent. . Example 1
In the same manner as in the above, the mixture of the lubricant and the fluidizing agent and the drug formulation components were continuously tableted using a three-layer tablet machine. Primary molding is 1
The tablet was pressed so as to have a hardness of 80 mg / tablet and a hardness of 1.5 kg. The secondary molded product was tableted so as to have a hardness of 205 mg / tablet and a hardness of 0.4 kg. Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was obtained at 25 ° C. and 82% RH.
, And dried in a box drier (45 ° C) for 5 hours to obtain an orally rapidly disintegrating tablet.

Example 12 160 parts by weight of mannitol and 5 parts by weight of nicergoline were mixed, and 40 parts by weight of sucrose was added to 25 parts by flow in a fluidized bed granulator.
% (W / w) aqueous solution and granulated, and the obtained granulated granules were used as drug formulation components. 10 parts by weight of magnesium stearate and 5 parts by weight of calcium stearate as a lubricant and microcrystalline cellulose (Avicel PH10) as a fluidizing agent
2: Asahi Kasei) (85 parts by weight) were mixed to prepare a mixture of a lubricant and a fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. The primary molded product was pressed at 180 mg / tablet and the hardness was 3 kg, and the secondary molded product was 205 mg / tablet.
Tablets were tableted to a hardness of 0.8 kg. Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was left overnight at 25 ° C. and 82% RH,
It was kept in a box dryer (45 ° C.) for 5 hours and dried to obtain a rapidly disintegrating tablet in the oral cavity.

[0114]

According to the method of the present invention, it is possible to stably supply a lubricant to a molding machine by mixing and using a lubricant and a fluidizing agent. Supplying a mixture of a lubricant and a fluidizing agent to a molding machine and molding (primary molding)
Then, since the lubricant remains in the molding machine even after discharging the primary molded product, if the drug prescription component is continuously molded (secondarily molded) by the molding machine after the primary molding, the molded product is molded. Molding can be performed without adhesion to the machine. Therefore, by alternately performing the primary molding and the secondary molding, efficient and continuous molding is possible without adding a lubricant to the drug formulation component.

Further, according to the present method, continuous molding is possible even if no lubricant is contained in the drug prescription component. Therefore, the disintegration and dissolution of the molded product by the lubricant is delayed. Since this method is completely absent, applying this method to the production of a rapidly disintegrating preparation in the oral cavity is extremely effective.

Continuation of the front page (51) Int.Cl. ⁷ Identification code FI A61K 47/36 A61K 47/36 47/38 47/38 (56) References JP-A-9-48726 (JP, A) JP-A-5-48 318198 (JP, A) JP 47-31827 (JP, B1) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 9/20 A61J 3/10 A61K 47/04 A61K 47/12 A61K 47/26 A61K 47/36 A61K 47/38

Claims (11)

(57) [Claims] Claims: 1. A formulation for oral administration as a lubricant and a glidant
Additive, and the angle of repose measured by the injection method is 6
A method for producing a molded product, comprising: molding a mixture with a powder having a temperature of 0 ° or less by a molding machine, discharging the molded product, and molding the drug prescription component by the molding machine. 2. The formulation additive for oral administration as a glidant is selected from crystalline cellulose, lactose, sucrose, mannitol, calcium phosphate and calcium citrate.
The method for producing a molded preparation according to claim 1, wherein the preparation is a kind or two or more kinds. 3. The method according to claim 1, wherein the lubricant is an alkaline earth metal stearate. 4. A product for oral administration as a lubricant and a fluidizing agent .
Mixing ratio of the agent additives, to lubricant 1 part by weight, preparation of molded preparation according to claim 1, 2 or 3, wherein a preparation for oral administration additive is 2 to 20 parts by weight of a fluidizing agent . 5. The method according to claim 1, wherein the molding machine is a multi-layer tablet machine or a multiple tablet machine. 6. A product for oral administration as a lubricant and a fluidizing agent .
Additive, and the angle of repose measured by the injection method is 6
A mixture with a powder having a temperature of 0 ° or less is molded by a molding machine, and after the molded product is discharged, the medicine is formed into the molding machine and a drug comprising a substance which is wettable so as to be moldable by humidification and which maintains its shape by drying after humidification A method for producing a rapidly disintegrating oral preparation, characterized in that a prescription component is supplied and molded, and the obtained molded product is humidified and then dried. 7. A product for oral administration as a lubricant and a fluidizing agent .
Additive, and the angle of repose measured by the injection method is 6
A mixture with powder having a temperature of 0 ° or less is molded by a molding machine, and after the molded product is discharged, a drug prescription component comprising a drug and an alcohol-soluble binder is supplied to the molding machine, and the molded product is molded. A method for producing a rapidly disintegrating preparation in the oral cavity, comprising: moistening the compound with alcohol, and removing the alcohol. 8. A method for producing a rapidly disintegrating oral preparation, comprising: moistening a molded product of a drug prescription component comprising a drug and an alcohol-soluble binder with alcohol, and removing the alcohol. 9. The method for producing a rapidly disintegrating oral preparation according to claim 7, wherein the drug formulation component contains sugar or (and) a sugar alcohol. 10. The method for producing a rapidly disintegrating oral preparation according to claim 7, wherein the alcohol-soluble binder is one or more selected from polyvinylpyrrolidone, hydroxypropylcellulose and ethylcellulose. 11. The method for producing a rapidly disintegrating oral preparation according to claim 7, wherein the alcohol is ethanol.