A tablet has an advantage of easy dosing and is the most preferable type for patient as oral administration and intrabuccal administration.
Such a tablet is generally produced by an internal lubricant method and an external lubricant spraying method.
According to the internal lubricant method, in order to prevent that molding material to be tabletted is apt to attach on punches and dies and gride between the punches and dies is apt to be caused so as to execute smooth tabletting and also prevent defective goods with sticking, capping or laminating, magnesium stearate, lauryl sodium sulphate, talc and so on are mixed in the molding material to be tabletted other than active compound and diluting agent and the mixture is compressed to obtain a tablet.
As an external lubricant spraying method, a tablet production method has been disclosed in, for example, JP-B-41-11273 and JP-A-56-14098.
FIG. 17 schematically shows procedures of the tablet production method disclosed in JP-B-41-11273.
According to the method comprised of charging a fixed amount of material to be tabletted in a die, tabletting the charged material in the die by means of a pair of an upper and a lower punches, and discharging the tablet, as a procedure before molding material is charged in the die 151 as shown in FIG. 17(a), a spray nozzle 159 for spraying lubricant L is provided above the die 151 and lubricant L is applied on a lower surface 153s of the upper punch 153 and an upper surface 154s of the lower punch 154, both of which are provided for the die 151 which comes to a place where the spray nozzle 159 is placed. Then molding material is charged in the die 151 as shown in FIG. 17(b), and the charged material m is compressed by means of the upper punch 153 on which lower surface 153s is applied with lubricant L and the lower punch 154 of which upper surface 154s is applied with lubricant as shown in FIG. 17(c).
The member indicated by the numeral 152 in FIG. 17 shows a rotary table provided with the die 151 (The same numeral is used in FIG. 18).
FIG. 18 shows a tablet production method described in JP-A-56-14098.
According to this method, before molding material is charged in a die 151, a spray 156 for spraying lubricant L and a nozzle 159 for spraying air are provided above the die 151. Lubricant L is sprayed in the spray 156 when the die 151 comes where the spray 156 is provided as shown in FIG. 18(a), lubricant is applied on an upper surface 154s of a lower punch 154 provided for the die 151 as shown in FIG. 18(b). As shown in FIG. 18(c), compressed air is sprayed on the lower punch 154 at a position where the nozzle 159 is provided, lubricant L applied on the upper surface 154s of the lower punch 154 is blown upwardly to be dispersed, then the dispersed lubricant L is attached on an inner wall 151s of the die 151 and a lower surface 153s of an upper punch 153. Thereafter, molding material m is compressed to produce a tablet by means of lubricated inner wall 151s of the die 151, lubricated lower surface 153s of the upper punch 153, and lubricated upper surface 154s of the lower punch 154.
However, some drugs are destabilized or dissolved or its elution becomes slow because its crystal is deformed by the pressure applied at the time of tabletting (usually 1 ton/c m2–2 ton/c m2), friction, and heating. (Hereinafter such substances are called “drugs which is denaturalized or inactivated when tabletted at high pressure” in this specification.)
As a method for tabletting such drugs, an internal lubricant method wherein lubricant such as macrogol 6000, sucrose esters of fatty acid, and so on are added to molding material has been already suggested. (Refer to the summary of 11th pharmaceuticals and powder design symposium, 79 (1994) and JP-A-8-175996.)
Solid dispersing pharmaceuticals wherein compound is dispersed in low molecular carrier or high molecular carrier has been recently developed.
Such solid dispersing pharmaceuticals are highly effective to heighten solubility of drugs which is slight soluble and has low absorbability into the body in case of oral dosage, to control releasing speed of drugs, and to improve bioavailability of drugs.
Solid dispersion pharmaceuticals are generally produced by a fusion method wherein drugs and carrier are heated and fused and thereafter cooled down. Or they are produced by means of a solvent method wherein drugs and carrier are dissolved in an appropriate solvent and the solvent is removed. Or they are produced by a fusion-solvent method wherein a fusion method and a solvent method are combined.
However, an internal lubricant means wherein a tablet including compound which are denaturalized or inactivated when tabletted at high pressure is produced by adding lubricant such as macrogol 6000, sucrose esters of fatty acid, and so on in molding material isn't an adequate method. According to drugs, compressed tablet may be destabilized or decomposed, or elution may become slow even if lubricant such as macrogol 6000, sucrose esters of fatty acid, and so on is added to molding material.
Further, depending on drugs, they may attach on punches and dies at the time of tabletting. As the result, produced tablet may cause sticking, capping and laminating.
When solid dispersion is produced into a tablet as solid dispersing pharmaceuticals wherein solid dispersion is pulverized into a suitable particle size and the pulverized substance and lubricant are mixed according to the prior internal lubricant method, property of the solid dispersion tablet may be changed because of water repellency of lubricant included in the tablet. When lubricant is included in the tablet, high pressure is required to give practical hardness. However, the solid dispersion may be denaturalized because of high tabletting pressure and originally designed property (for example disintegrating time) isn't achieved.
Therefore, pharmaceuticals including drugs which are denaturalized or inactivated when tabletted at high pressure and solid dispersing pharmaceuticals are generally supplied as capsule in the market so far.
However, capsule is hard to be taken for elderly person and children because it floats on the water when taking with water. It has been requested by physician and so on to develop a tablet which sinks in the water and is easy to be swallowed when taking with water as pharmaceuticals including drugs which are denaturalized or inactivated when tabletted at high pressure and as solid dispersing pharmaceuticals.
Also capsule needs a body and a cap and its production takes a lot of labor as follows. Drugs which are denaturalized or in activated when tabletted a thigh-pressure and solid dispersion (powder and granule) are pulverized and charged in the body of capsule and the cap is covered thereon to be sealed.
Further, physician requests not only that pharmaceuticals conventionally supplied as capsule in the market is produced as a tablet but also that such tablet is dividable so that patient can take appropriate dosage.
The present invention has been developed in order to solve the above-mentioned problems. The object of the present invention is to provide a production method of tablet wherein a tablet including compound powdered or granulated which is denaturalized or inactivated when tabletted at high pressure can be easily produced without denaturalizing or deactivating such compound.
Another objet of the invention is to provide a tablet including solid dispersion powdered or granulated keeping function of the solid dispersing material, a tablet including compound which is denaturalized or inactivated when tabletted at high pressure without denaturalizing or deactivating such compound, and a dividable type tablet of these tablets which can keep its function when divided.
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USPTO Backgrounds