JPS584573B2 - Zoryubutsunoseihou - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing granules of relatively low molecular weight water-soluble substances.

More specifically, the present invention relates to a crystal or crystalline powder substance with a molecular weight of 500 or less, in which 1 g of the substance is 1 ml or more.
The present invention relates to a method for producing a granulated material having the property of dissolving in less than 0 ml of water by a fluidized bed granulation method.

BACKGROUND ART In recent years, methods of forming various chemical substances into granules have been widely put into practical use in the fields of pharmaceuticals, agricultural chemicals, foods, and the like.

However, if the substance to be granulated is a crystalline substance or crystalline powder substance with a relatively small molecular weight and relatively high solubility in water, it is necessary to maintain the hardness of the granulated material. The bonding force between material particles alone was insufficient, and the use of a binder was considered essential.

In particular, with the development of granulation technology in recent years, the processes of conventional granulation technology, namely, the mixing process of powdering ingredients, the kneading process of the mixture and connective tissue, the granulation process, and the drying process, have been integrated into one machine. A continuous fluidized bed granulator was devised and put into practical use.

The production of granulated products using this fluidized bed granulator involves fluidizing the raw material (powder) to be granulated by blowing air, spraying it with a solution containing a binder, and then drying it. However, when flowing, the granules are subjected to various impacts, and if the bonds between the powder particles are weak, the granules cannot maintain their shape, and the granules wear out. resulting in loss of material.

Further, even after the granules have been made into a product, it is most undesirable for the granules to be destroyed or worn out during transportation and storage.

Therefore, it is essential to use an appropriate binder during granulation.

Conventionally, water-soluble high-density substances have been cited as substances frequently used as seed binders, but natural polymer substances,
For example, gum acacia, starch, pectin, gum tragacanth, agar, dextrin, gelatin, etc. are not desirable due to concerns of uncertain quality and contamination with impurities; generally, polyvinylpyrrolidone, polyvinyl algol, psidium carboxymethylcellulose, methylcellulose,
Semi-synthetic or synthetic polymeric materials such as hydroxypropylcellulose are used as preferred binders.

The use of these binders increases the impact resistance of the granules during their production, and increases their fracture resistance and abrasion resistance during handling after they are made into products. At times, this becomes a factor that impedes collapse and dispersion.

Therefore, in the production of granules that are desired to disintegrate rapidly during use, a binder that satisfies these two contradictory requirements is particularly required.

Particularly in medicines, where early onset of drug efficacy is required, the dissolution rate must be increased, and disintegration property is also a required element.

In this respect, conventional polymer binders do not meet this requirement at all, and no binder that meets this requirement has yet been found.

In other words, conventionally used polymer binders function effectively in slowing down the elution rate of granulated components and delaying the onset of drug efficacy, but there is a need for rapid disintegration and acceleration of the elution rate. On the contrary, it was a negative factor.

Moreover, the use of synthetic or semi-synthetic polymeric substances poses the difficult problem of always requiring safety within the human body.

The present inventors have arrived at the present invention as a result of conducting various studies on granulation methods for specific substances in the presence of various problems in these conventional techniques.

That is, the purpose of the present invention is to use a binder when the substance to be granulated necessarily requires a binder for granulation, and it is extremely difficult to select the binder. The object of the present invention is to provide a method for producing granulated products that eliminates the problems of the prior art as described above.

The present invention provides a method for producing granules of crystals or crystalline powder substances having a molecular weight of 500 or less and having the property that 1 g of the substance dissolves in 1 ml or more and less than 30 ml of water using the fluidized bed granulation method. It is.

The feature of the method of the present invention is that in producing the above granulated product, a mixture solution of the substance to be granulated, lactose and water is used as a binder, and the substance to be granulated and lactose are combined with a binder as a binder. The purpose is to granulate the mixture.

It is surprising that due to these characteristics, it is possible to produce a granulated material without using a conventional binder, and the material has properties that cannot be granulated without a binder.

What is even more surprising is that the granules obtained by the method of the present invention have extremely low abrasiveness, yet have extremely high disintegration properties and runoff rates during use.

In the method of the present invention, the substance to be granulated has a molecular weight of 50
0 or less crystals or crystalline powder substances, the substance 19
These specific conditions have the following technical meaning.

That is, since the viscosity of an aqueous solution of a compound having a relatively large molecular weight is generally high, it is not necessary to use a binder in the production of granules, or there is no difficulty in selecting a binder.

On the other hand, if the molecular weight is relatively small, it is impossible to obtain granules that can withstand practical use without the use of a binder. The relationship between the properties of the binder and the properties of the substance to be granulated in relation to the purpose of use and desired effect of the product (product), and the effect that the properties of the binder itself have on the product use, etc. The selection of the type becomes extremely difficult.

Therefore, it will be understood that the target substance of the method of the present invention is a substance with a relatively small molecular weight, and the stipulation that the molecular weight is 500 or less is a condition indicating the standard.

Next, the target substance of the method of the present invention is a substance that has the property that 1 g of the substance dissolves in 1 ml or more and less than 30 mA of water.

Substances that are more soluble in water than this are those that allow production of granules that can withstand practical use without a binder.
Substances that are less soluble than these, which can be the object of the present invention, are also not possible because they cannot themselves be granulated by the method of the present invention.

The above-mentioned conditions regarding solubility in water correspond to "easily soluble in water" and "slightly soluble" in the Eighth Edition Japanese Pharmacopoeia.

Furthermore, the target substance of the method of the present invention is a crystal or crystalline powder substance, and this means that the crystalline substance or crystalline powder substance as defined above is generally difficult to granulate due to its interfacial properties, and it is difficult to granulate it. It will be appreciated that in view of the need for a binder, it may be a subject matter for the purpose of the present invention.

The method of the present invention makes it possible to maintain resistance to breakage and abrasion of granules without using a polymeric binder, and to prevent disintegration during use without using a disintegrant to accelerate disintegration. It is possible to obtain a granulated product that completely satisfies the two contradictory requirements of being able to easily produce granules.

One embodiment of the method of the present invention will be described below with reference to Examples, but it goes without saying that the objects and effects of the present invention are not limited to these Examples.

Example Sodium carbazosulfonate 100mg and lactose 900mg
After mixing for 10 minutes with a fluidized bed granulator, 24 parts of this mixture was added with 36 parts of distilled water, and completely dissolved at 60°C.

The resulting solution is used as a binder.

The remaining part of the mixture described above is placed in a fluidized bed granulator and fluidized, and the binder prepared above is sprayed onto it, followed by granulation and drying.

The yield of the obtained granules was 95 for those with a size of 100 to 350μ.
%, and its friability is 0. 2%, angle of repose is 38°
, the outflow rate (g/min) is 17. It was 90.

The dissolution rate of sodium carbazochrome sulfonate in the obtained formulation product was measured using a basket wire mesh 1 according to the method of the United States Pharmacopoeia
By placing 70 mg of the above preparation into a basket and measuring the time required for 100% of the drug in the preparation to be eluted, using the 8th edition Japanese Pharmacopoeia artificial gastric juice liquid 1 as the test liquid. Tested.

The result was 1 minute 40 seconds.

Although this preparation does not contain any additives other than lactose, it exhibits excellent dispensing properties, rapid disintegration, and rapid dissolution rate, and has extremely low friability.

Claims (1)

[Claims] 1. A method for producing granules of crystals or crystalline powder substances with a molecular weight of 500 or less, which have the property of dissolving in 1 ml or more and less than 30 ml of water, in which 1 g of the substance has a property of dissolving in 1 ml or more and less than 30 ml of water. A fluidizing method characterized in that a solution of a mixture of the substance to be granulated, lactose and water is used as a binder, and the mixture of the substance to be granulated and lactose is granulated using the binding agent. A method for producing a granulated product using a layer granulation method.