6-Fluoro-3-hydroxy-2-pyrazinecarboxamide (hereinafter, it will be referred to as the compound A) or a salt thereof is a compound which is useful as a treatment such as prevention or therapy of a viral infection or, particularly, an influenza viral infection [Patent Document 1].
One to several tablet(s) containing the compound A or a salt thereof is/are administered per os. For improving the drug compliance, there has been a demand for a tablet where numbers of tablets to be administered are reduced and ingestion thereof is easy. Thus, there has been a demand for a development of a tablet where the amount of the compound A or a salt thereof contained therein is high and the size of the tablet is in a size of being able to be easily ingested.
There has been also a demand for a mixed powder for tableting for the manufacture of the tablet as such.
In the manufacture of tablets, it is essential that the mixed powder for tableting has a compression molding property. When the compression molding property of the mixed powder for tableting is low, hardness of the tablet becomes low. In that case, there is a possibility that the tablets are broken upon packaging or during transportation or that the tablets are worn away or cracked in a coating machine upon subjecting the tablets to film coating.
On the other hand, when the cohesive force of the mixed powder for tableting is strong, fluidity is poor and it is difficult to provide a predetermined amount of the mixed powder for tableting to a mortar upon tableting. Therefore, discrepancies in the tablet masses become large and quality is deteriorated.
It has been reported already that the size of an easily ingestible circular tablet has a diameter of 7 to 8 mm and that the size of an easily ingestible elliptic tablet has a long diameter of 9 mm [Non-Patent Document 1]. A tablet in a big size is hardly ingestible due to the resisting feel and the compressive feel not only for small children and patients having a difficulty in swallowing but also for ordinary adult patients, and causing the lowering of the drug compliance. Size of a tablet is preferred to be not larger than 9 mm.
The compound A or a salt thereof has such a property that no compressive molding property is available, specific volume is big, cohesive force is strong and fluidity is low. It is difficult that a tablet containing a large amount of the compound A or a salt thereof and being in an easily ingestible size is manufactured by a conventional method.
There has been reported a method where an additive having a high molding property such as crystalline cellulose is compounded to manufacture a mixed powder for tableting having a high compressive molding property whereby a tablet having a necessary hardness is prepared [Non-Patent Document 2].
However, in order to manufacture a tablet containing the compound A or a salt thereof where the necessary hardness is available, it is necessary that the amount of the additive contained therein is not less than 50% or, preferably, not less than 60% of the mass of the tablet. Due to such a reason, the size of a tablet becomes big.
As to a method where the cohesive force of the mixed powder for tableting is lowered and the fluidity is enhanced, there has been reported a method where a fluidity promoter is compounded [Non-Patent Document 3].
However, it is not possible to improve the cohesive force of the compound A or a salt thereof only by means of compounding a fluidity promoter. The mixed powder for tableting having poor fluidity shows a poor charging property into a mortar upon tableting. Therefore, discrepancies in the tablet masses become big and quality is deteriorated.
On the other hand, there has been known a method in which a binder is used and granulation is carried out by means of a dry or a wet granulation method whereby the bonding strength among the particles upon tableting is enhanced. However, although the necessary hardness is achieved by this method, the dissolution property lowers due to the rise in the bonding strength among the particles.
Up to now, there has been known no tablet in which the amount of the compound A or a salt thereof contained therein is high, the size is an easily ingestible size, the dissolution property is excellent and the hardness is durable against film coating, packaging and transportation whereby the tablet is stable for a long period of time.
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