JP2003210553A - Preparation molding device and preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To further improve anticorrosion of parts of a preparation molding device in the molding of the preparation by the compression molding of corrosive materials. <P>SOLUTION: The preparation molding device 1 which performs compression molding of the material a comprising corrosive granules or powders to mold preparation a' comprises the second table 12 on which are formed a hopper 20 for storing the material (a) and a quantitative container 16 for conveying the material (a) stored in the hopper 20 by a fixed amount each, the first table 11 on which is formed a mortar 15 for molding the preparation a', a filling bottle 26 for filling the mortar 15 with the material (a) stored in the hopper 20 by a fixed amount each, pestles 32 and 33 which mold the preparation a' by compressing the material (a) filled into the mortar 15, and a takeoff pin 42 for taking the preparation a' out of the mortar 15. At least one of the hopper 20, the quantitative container 16, the mortar 15, the filling pin 26, the pestles 32 and 33 and the takeoff pin 42 is made of a metal such as Ti or the surface thereof is coated with a diamond-like C or the like. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a formulation molding apparatus for compressing and molding a corrosive raw material to mold a formulation and its parts, and further to a formulation molded by this formulation molding apparatus and a molding method thereof.

[0002]

2. Description of the Related Art In general, a preparation is manufactured by filling raw materials such as granules and powders stored in a hopper into a die in a fixed amount and compression-molding them with a punch. Parts such as hoppers, mortars, and punches that come into contact with the raw materials that are provided in the formulation molding device are usually made of metal, so it is difficult to avoid rust and corrosion. For this reason, oily substances are applied to the surfaces of parts that come into contact with the raw materials in the formulation molding device, or surface treatment is performed with fluororesin or the like.

[0003] Here, in the case of a compressed tablet in which the raw material is moistened more than usual in the raw material at the time of molding and compression is performed, high pressure is not applied at the time of production, and after drying a wetting agent such as water or ethanol. Since it has a proper space inside,
It has excellent disintegration and dissolution properties and is easy for the elderly and children to take. However, when molding these tablets, it is p
Due to the effect of H, the parts that come into contact with the raw materials are easily corroded.

Therefore, in Japanese Patent Laid-Open No. 64-27798,
A compression-molding machine for tablets with corrosion resistant amorphous coating is disclosed. Further, Japanese Patent Application Laid-Open No. 11-158571 discloses a mold for compression molding in which at least one of tantalum and niobium is added to cobalt, chromium, tungsten and carbon. Also, Japanese Patent Laid-Open No. 2001-7118
No. 9 discloses a punch for tabletting coated with chrome dope-N. In addition, Japanese Patent Laid-Open No. 2001-6259
No. 5 discloses a punch and die for tableting, which are made of a Ni-Cr-Al alloy. In addition, JP 2001-1
No. 078 discloses a tableting die and punch using SKD11 as a material.

On the other hand, a device for molding so that the raw material does not directly contact the parts has been developed. For example, JP-A-8
No. -19589 discloses a device in which a moist powder is filled in a tablet molding hole and at least one surface of the moist powder is molded into a tablet by a molding die through a film. Further, JP-A-8-19590 discloses a device for molding a container using a resin film, filling the container with wet powder, and tableting.

[0006]

[Patent Document 1] Japanese Patent Laid-Open No. 64-27798

[Patent Document 2] Japanese Patent Laid-Open No. 11-158571

[Patent Document 3] JP 2001-71189 A

[Patent Document 4] Japanese Patent Laid-Open No. 2001-62595

[Patent Document 5] Japanese Patent Laid-Open No. 2001-1078

[Patent Document 6] JP-A-8-19589

[Patent Document 7] Japanese Patent Laid-Open No. 19590/1996

[0007]

However, even if these conventional apparatuses are used, it is difficult to sufficiently prevent deterioration and corrosion of a die, a punch or the like in contact with the raw material.

[0008] Therefore, the present invention is to further improve the corrosion resistance of the components of the formulation molding device when the corrosive raw material is compression molded to mold the formulation.

[0009]

Means for Solving the Problems As a result of intensive studies by the present inventors, the above problems can be solved by using a specific metal or alloy as a material, or by using a coating of diamond-like C or the like. The present invention has been completed and the present invention has been achieved. That is, the present invention relates to a component which is in contact with the above-mentioned raw material in a formulation molding apparatus for compressing and molding a raw material composed of corrosive granules or powders, the component being Ti, Ti alloy,
It is a component of a pharmaceutical molding apparatus, which is formed of one or more metals selected from the group consisting of Ni-Cr-Mo alloys, Ni-Mo alloys, and Co-based alloys. The present invention also relates to a diamond-shaped C or T component which is a component in contact with the raw material in a pharmaceutical molding apparatus for compressing and molding a raw material made of corrosive granules or powder to mold the pharmaceutical preparation.
i, a component of a pharmaceutical molding apparatus, the surface of which is coated with any one of double coating of titanium nitride, chromium nitride and Ti-titanium nitride. The parts are, for example, a hopper for storing the raw material, a quantitative container for quantitatively conveying the raw material, a die for molding the formulation, a filling pin for filling the die with the granules or powder,
A punch for molding the formulation, a take-out pin for removing the formulation from a die in which the formulation is molded, and the like. When the surface is coated with any one of the diamond-like C, Ti, titanium nitride, chromium nitride and Ti-titanium nitride double coatings, the parts are steel, copper, SUS.
And so on.

Further, the present invention is a formulation molding apparatus for compressing and molding a raw material made of corrosive granules or powders, and a hopper for storing the raw material and a die for molding the formulation. A first table in which the mortar is formed, a filling pin that fills the mortar with the raw material stored in the hopper in a fixed amount, a punch that compresses the raw material filled in the mortar to mold the formulation, and the mortar And a take-out pin for taking out the preparation from the hopper, wherein at least one of the hopper, the die, the filling pin, the punch and the take-out pin is made of Ti, Ti alloy, Ni-Cr-Mo alloy, N.
characterized by being formed of one or more metals selected from the group consisting of i-Mo alloys and Co-based alloys,
It is a pharmaceutical molding device. Further, the present invention is a formulation molding apparatus for compressing and molding a raw material composed of corrosive granules or powders, and forming a hopper for storing the raw material and a mortar for molding the formulation. A first table, a filling pin for filling the mortar with the raw material stored in the hopper in fixed amounts, a punch for compressing the raw material with which the mortar is filled to mold the formulation, and the formulation from the mortar And a take-out pin for taking out, wherein at least one of the hopper, the die, the filling pin, the punch and the take-out pin is a double layer of diamond-like C, Ti, titanium nitride, chromium nitride and Ti-titanium nitride. It is a drug product forming device characterized in that the surface is coated with one of the coats. It is preferable to include a second table in which a quantitative container for transporting the raw material stored in the hopper by a fixed amount is formed. In that case, the quantitative container is made of Ti, Ti alloy, Ni-Cr-Mo alloy, Ni.
It is preferably formed of one or more metals selected from the group consisting of —Mo-based alloys and Co-based alloys. Further, the surface of the quantitative container may be coated with any one of diamond C, Ti, titanium nitride, chromium nitride and Ti-titanium nitride double coating. When the surface is coated with any one of the diamond-like C, Ti, titanium nitride, chromium nitride and Ti-titanium nitride double coats, the hopper, the die, the filling pin, the punch, the take-out pin, The quantitative container is
It may be steel, copper or SUS.

Further, the present invention is a method for molding a formulation by compressing and molding a raw material consisting of corrosive granules or powders by means of this formulation molding device, which comprises a step of filling the raw material in a fixed amount in a die, A molding method comprising: a step of compressing the raw material filled in to mold the preparation; and a step of removing the preparation from the die.
The raw material may contain an acidic drug and salts thereof, an inorganic acid salt of a basic drug or an organic acid salt of a basic drug. The acidic drug and salts thereof are, for example, any of ascorbic acid, calcium ascorbate, nicotinic acid, salicylic acid, acetylsalicylic acid, sodium valproate, sodium azulene sulfonate, and diclofenac sodium. Examples of the inorganic acid salt of the basic drug include thiamine hydrochloride, riboflavic acid phosphate, pyridoxine hydrochloride, pyridoxal phosphate, pyridoxal hydrochloride,
Meclizine hydrochloride, scopolamine hydrobromide, methylephedrine hydrochloride, dihydrocodeine phosphate, ranitidine hydrochloride, berberine chloride, etilefrine hydrochloride, fursultiamine hydrochloride, loperamide hydrochloride, donepezil hydrochloride, oxybutynin hydrochloride, propiverine hydrochloride, nicardipine hydrochloride, manidipine hydrochloride, hydrochloric acid Benidipine, diphenidol hydrochloride,
Diphenylpyraline hydrochloride, diphenhydramine hydrochloride, promethazine hydrochloride, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, methylatropine hydrochloride, papaverine hydrochloride, loperamide hydrochloride, cetirizine hydrochloride. The organic acid salt of the basic drug is, for example, any of chlorpheniramine maleate, enalapril maleate, diphenhydramine salicylate, ergotamine tartrate, bromoclybutine mesylate, amethinium methylsulfate, ketotifen fumarate, and fluvoxamine maleate. Further, the formulation may be a mold tablet.

The present invention also provides a formulation molded using this formulation molding apparatus. Further, the present invention is a formulation molded by this molding method. The formulation may be a molded tablet.

Incidentally, Ti is obtained from, for example, Daido Steel Co., Ltd.
Ti sold under the trade names of DT-1, DT-2, DT-3, etc. can be used. Ti alloys are Ti-6Al-4V, Ti-3Al-2.
5V, Ti-6Al-7V-0.5Ta, Ti-4.5Al-3V-2Fe-2Mo, Ti-15V-3
Cr-3Sn-3Al, Ti-20V-4Al-1Sn, Ti-22V-4Al, Ti-16V-4Sn
-3Al-3Nb or the like, and for example, a Ti alloy sold by Daido Steel Co., Ltd. under the trade name of DAT-5, DAT-5E, DAT-52, etc. can be used. Ni-Cr-Mo alloy is Ni-5Fe-16C
r-16Mo, Ni-4Fe-22Cr-13Mo, Ni-19Cr-19Mo, Ni-28Cr-18
Mo, Ni-30Cr-20Mo, etc., such as MAT-21, MA53C, M
Ni-Cr-Mo alloys sold under the trade name of A55C, Hastelloy C-276, Hastelloy C-22 and the like can be used. Ni-Mo alloy is Ni-5Fe-28M
o, Ni-28Mo, Ni-1.5Fe-1.5Cr-28.5Mo, etc., for example, Ni-Sold by Mitsubishi Materials Corp. under the trade names Hastelloy B, Hastelloy B-2, Hastelloy B-3. Mo-based alloys can be used. Co-based alloys are, for example, 9Ni-
3Fe-26Cr-5Mo, etc., for example, Co sold by Mitsubishi Materials Corporation under the trade name of Ultimate Alloy
Base alloys can be used. In addition, it is also conceivable to use a Ni-Cr-based alloy or a Ni-Cr-Mo-Fe-based alloy as the metal forming at least one of the hopper, the die, the filling pin, the punch, and the ejection pin.
In this case, the Ni-Cr alloy is Ni-45Cr-1Mo, and Ni-Cr alloy sold by Mitsubishi Materials Corp. under the trade name of MC alloy can be used. Ni-Cr-Mo-Fe alloys are Ni-15Fe-30Cr-5Mo, etc., and Ni-Cr-Mo-Fe alloys sold by Mitsubishi Materials Corporation under the trade name Hastelloy G-30. Alloys can be used. The chromium nitride coating can be performed by coating the substrate with chromium nitride by a known method, for example, a low temperature physical vapor deposition method. For example, it can be based on the product sold under the trade name of Celtes N by Nanocoat TS Co., Ltd.

The formulation means tablets, chewable agents, molding agents, caplets, fast-disintegrating tablets, fast-dissolving tablets, troches and the like. These preparations can be used as medicines, quasi drugs, foods, agricultural chemicals, fertilizers and the like.

In the present invention, the raw material consisting of corrosive granules or powders is an active substance exhibiting acidity or alkalinity, preferably acidic drugs and salts thereof, inorganic acid salts of basic drugs or basic drugs. Contains an organic acid salt. These include pharmacologically acceptable salts, hydrates and derivatives thereof.

[0016] As a compounding substance of the preparation, in addition to the raw material (main ingredient) consisting of corrosive granules or powders, various additives may be added if necessary. The additive is not particularly limited,
It means an additive used when formulating a drug, a quasi drug, etc., and an appropriate one may be appropriately selected depending on the type of main agent, dosage form and the like. Examples of additives include excipients,
Binder, disintegrant, lubricant, superplasticizer, coating agent,
Examples thereof include suspending agents, emulsifying agents, stabilizing agents, flavoring agents, flavoring agents and fragrances. Examples of the excipient include lactose, crystalline cellulose, D-mannitol, corn starch and the like. Examples of the binder include hydroxypropyl cellulose, hydroxypropylmethyl cellulose, povidone, polyvinyl alcohol and the like. Examples of the disintegrant include corn starch, carmellose calcium, croscarmellose sodium, crospovidone and the like. As a lubricant,
Magnesium stearate, calcium stearate,
Examples include talc. Examples of the fluidizing agent include light silicic acid anhydride, talc, hydrous silicon dioxide and the like. Examples of the coating agent include hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose phthalate, ethyl cellulose and the like. Examples of the suspending agent include sodium alginate, carmellose sodium, methyl cellulose and the like.
Examples of the emulsifier include glyceryl monostearate and sucrose fatty acid ester. Examples of the stabilizer include sulfite, tocopherol, dibutylhydroxytoluene and the like. As a corrigent, sucrose, D-sorbitol, xylitol, maltitol,
Examples include sucralose, aspartame, stevia sweetener, acesulfame potassium and the like. As a flavoring agent / fragrance, orange essence, caramel, menthol,
Sugar flavor etc. can be illustrated.

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION Preferred embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is a plan view of a drug product molding apparatus 1 according to an embodiment of the present invention. Figure 2
[Fig. 2] is a front view of the formulation molding apparatus 1 as viewed from below in Fig. 1. FIG. 3 is a right side view of the formulation molding apparatus 1 as viewed from the right in FIG.

Device body 1 incorporating a drive mechanism such as a motor
On the upper surface of 0, a large-diameter first table 11 and a small-diameter second table 12 are both horizontally arranged. The upper end of the rotary drive shaft 13 projecting upward from the upper surface of the device body 10 is attached to the center of the lower surface of the first table 11, and similarly, the upper surface of the device body 10 is attached to the upper surface of the second table 12 at the center of the lower surface. The upper end of the rotary drive shaft 14 projecting to is attached. These rotary drive shafts 13, 14 are driven by a drive mechanism such as a motor (not shown) built in the apparatus body 10.
The first table 11 and the second table 12 are shown in FIG.
In the above, all of them rotate intermittently in the clockwise direction. However, the first table 11 rotates by 45 °, while the second table 12 rotates by 90 °, and while the first table 11 rotates once,
The table 12 is adapted to rotate twice.

The second table 12 is arranged above the first table 11, and at the station B shown in FIG. 1, the second table 1 is placed on the first table 11.
2 are arranged so as to partially contact and overlap. The first table 11 is provided with two mortar units 15 at each of eight circumferentially divided positions (intervals at which the central angle is 45 °), and the second table 12 is provided with: Two quantification containers 16 are provided at positions (intervals having a central angle of 90 ° each) divided into four equal parts in the circumferential direction. In the embodiment of the present application, the mortar 15 and the quantitative container 16 are formed as through holes in the disk-shaped first table 11 and the second table 12, respectively, and both the mortar 15 and the quantitative container 16 have the same diameter. It is a circular hole. Further, the positions of the first table 11 and the second table 12 are set so that the mortar 15 overlaps just below the fixed quantity container 16 at the position of the station B. As described above, with the intermittent rotation of the first table 11 and the second table 12, the first table 1
The mortar 15 is divided into 8 equal parts, and two mortars 15 are installed one after another 45 °
In addition to moving intermittently, the fixed quantity containers 16 are equally divided into four and are provided on the second table 12 at intervals of 90 °.
The mortar 15 is always positioned below the fixed quantity container 16 and is moved sequentially.

A hopper 20 is arranged above the second table 12 at a position of the station A on the second table 12 which is 180 ° opposite to the station B. In the hopper 20, corrosive granules or powders, which are the raw material a for molding the preparation, are put. Although the lower end of the hopper 20 has an opening, the second table 12
Is blocked by the upper surface of.

Along with the intermittent rotation of the second table 12 described above, the fixed quantity containers 16 provided on the second table 12 are divided into four equal parts, and two fixed quantity containers 16 are intermittently moved by 90 °, and the position of the station A is changed. In the above, the fixed quantity container 16 is always positioned at the lower end of the hopper 20 and sequentially moved. Then, at the position of station A, the fixed quantity container 16 that has moved to the lower end of the hopper 20 in this way.
A predetermined amount of the raw material a is dropped from the inside of the hopper 20 by its own weight and filled. In this way, the raw material a filled in the fixed quantity container 16 at the station A is sequentially moved to the station B with the intermittent rotation of the second table 12.

As described above, the mortar 15 is placed below the metering container 16.
At the station B where the
5 is arranged above the second table 12. As shown in FIG. 4, on the lower surface of the filling and pressurizing device 25, the fixed quantity container 16 and the mortar 15 positioned at the station B and stopped.
A pair of filling pins 26, which are located just above, are extendably provided. The filling pin 26 includes the metering container 16 and the mortar 1.
It has a cylindrical shape with a diameter slightly smaller than the inner diameter of 5. Then, as shown in FIG. 5, when the filling pin 26 extends downward by the operation of the filling pressurizing device 25, the lower end of the filling pin 26 descends in the fixed quantity container 16 and the raw material filled in the fixed quantity container 16 is reached. The a is pushed down into the die 15.

In FIG. 1, at a position of a station C rotated 90 ° in a clockwise direction from the station B of the first table 11, an upper molding device 30 and a lower molding device 30 are arranged so as to face each other with the first table 11 interposed therebetween. A device 31 is arranged. With the intermittent rotation of the first table 11 described above, two mortars 15 which are equally divided into two and are provided on the first table 11 are provided in each of the upper molding device 30 and the lower molding device 31 arranged at the station C. It is arranged so that it is intermittently positioned and moved between them. With this,
At the above-mentioned station B, the mortar 1 is removed from the fixed quantity container 16
The raw material a filled in 5 is sequentially moved to the station C.

As shown in FIG. 6, a pair of upper punches 32 are provided on the lower surface of the upper molding device 30 so as to be extendable, and a pair of lower punches 33 are extendable on the upper surface of the lower molding device 31. It is provided. The upper punch 32 is positioned just above the mortar 15 which is positioned and stopped at the station C, and the lower punch 33 is positioned just below. The upper pestle 32 and the lower pestle 33 have a cylindrical shape with a diameter slightly smaller than the inner diameter of the die 15. Then, as shown in FIG. 7, the upper punch 32 is extended downward by the operation of the upper molding device 30, and at the same time, the lower punch 33 is extended upward by the operation of the lower molding device 31, so that the upper punch 32 is moved upward in the die 15. The raw material a is compression-molded between the lower end of the punch 32 and the upper end of the lower punch 33. By being compression-molded in this way, the formulation a ′ is manufactured in the die 15.

At the position of the station D on the opposite side of the station B by 180 ° in the first table 11 (the position further rotated by 90 ° in the clockwise direction from the station C in FIG. 1), the drying device 35 is placed. It is arranged around the first table 11. With the intermittent rotation of the first table 11 described above, the mortar 15 which is divided into eight equal parts on the first table 11 and is provided two by two passes through the drying device 35 arranged at the station D sequentially. It has become. Along with this, the mortar 1 at the above-mentioned station C
The formulation a'compressed and molded in 5 is dried while passing through the station D while being held in the die 15.

In FIG. 1, at the position of station E, which is further rotated by 90 ° in the clockwise direction from station D, the take-out device 40 is arranged above the first table 11 and the starting end of the conveyor 41 is located below. It is arranged. With the intermittent rotation of the first table 11 described above, the first
The mortar 15 is divided into eight equal parts on the table 11
However, these take-out devices 40 arranged at the station E
And the conveyor 41 start end portion are sequentially positioned and moved intermittently. Along with this, the formulation a ′ dried in the above-mentioned station D while being held in the die 15 is sequentially moved to the station E.

As shown in FIG. 8, a pair of take-out pins 42 are provided on the lower surface of the take-out device 40 so as to extend freely.
The take-out pin 42 is positioned just above the mortar 15 positioned and stopped at the station E. The take-out pin 42 has a cylindrical shape with a diameter slightly smaller than the inner diameter of the die 15. Then, as shown in FIG. 9, when the take-out device 40 is operated, the take-out pin 42 extends downward, so that the lower end of the take-out pin 42 is moved to the mortar 1.
The formulation a ′ that has been held in the mortar 15 down to 5 is dropped from the mortar 15 and transferred onto the upper surface of the starting end of the conveyor 41.

The conveyor 41 is adapted to sequentially convey the formulation a ′ thus placed at the starting end to the outside of the formulation molding apparatus 1.

In the formulation molding apparatus 1 as described above, the hopper 20, which is a part in contact with the raw material a, and the second table 1
2, a filling container 26 of the filling and pressurizing device 25, a die 15 provided on the first table 11, an upper punch 32 of an upper molding device 30 and a lower punch 3 of a lower molding device 31.
3, at least one of the take-out pins 42 of the take-out device 40 is made of Ti, Ti alloy, Ni-Cr-Mo alloy, Ni-
1 selected from the group consisting of Mo-based alloys and Co-based alloys
It is made of at least one kind of metal (hereinafter referred to as "Ti alloy etc."). Alternatively, in the formulation molding apparatus 1 as described above, the hopper 20, which is a component in contact with the raw material a, the fixed quantity container 16 provided on the second table 12, and the filling / pressurizing device 25.
Filling pin 26 of the mortar 1 provided on the first table 11
5, Upper punch 32 of upper molding device 30 and lower molding device 31
At least one of the lower punch 33 and the take-out pin 42 of the take-out device 40 has a double coat of diamond-like C, Ti, titanium nitride, chromium nitride and Ti-titanium nitride (hereinafter,
The surface is coated with either "diamond-like C" or the like).

In the formulation molding apparatus 1, first, at the position of the station A, a predetermined amount of the raw material a is dropped from the hopper 20 by its own weight into the fixed quantity container 16 which is positioned and moved to the lower end of the hopper 20. And then filled. In this way, the raw material a filled in the fixed quantity container 16 at the station A sequentially moves to the station B with the intermittent rotation of the second table 12. In this case, if the hopper 20 that is a part in contact with the raw material a is formed of a Ti alloy or the like, or if the surface is coated with diamond-like C or the like, it is possible to prevent the hopper 20 from being corroded by the raw material a. .

Next, the raw material a thus filled in the fixed quantity container 16 at the station A is stored in the second table 12
It moves to station B in sequence with intermittent rotation.
In this case, the fixed quantity container 16 which is a part in contact with the raw material a is T
If the raw material a is formed of i alloy or the like and the surface thereof is coated with diamond-like C or the like, the fixed quantity container 16 is corroded by the raw material a even while the raw material a is moved from the station A to the station B. Can be prevented. During the movement from station A to station B, a fixed amount container 16 is attached by a holding member (not shown) closely attached to the lower surface side of the second table 12.
The lower part of the container is closed to prevent the raw material a from dropping from the fixed quantity container 16.

Next, the metering container 16 moves to the station B by the intermittent rotation of the second table 12, and at the same time, the mortar 15 is positioned below the metering container 16. Then, as described above with reference to FIG. 5, the filling pin 26 extends downward due to the operation of the filling pressurizing device 25 and the fixed quantity container 1
Raw material a, which has descended in 6 and has been filled in the quantitative container 16
Is pushed down into the mortar 15. In this way, a predetermined amount of the raw material a is filled in the die 15. In this case, if the filling pin 26 or the die 15 that is a part in contact with the raw material a is formed of a Ti alloy or the like, or if the surface is coated with diamond-like C or the like, the filling pin 26 and the die 15 are the raw material a. Can be prevented from being corroded by.

Next, the raw material a thus filled in the die 15 at the station B is sequentially moved to the station C with the intermittent rotation of the first table 11. In this case, if the die 15 that is a part in contact with the raw material a is formed of Ti alloy or the like, or if the surface is coated with diamond-like C or the like, the raw material a is moved from the station B to the station C in this way. Even in the interval, the mortar 15 can be prevented from being corroded by the raw material a. During the movement from the station B to the station C, the lower side of the mortar 15 is closed by a pressing member (not shown) closely attached to the lower surface side of the first table 11, so that the raw material a from the mortar 15 is removed. Falling is prevented.

Next, when the raw material a is moved to the station C in this way, as described above with reference to FIG. 7, the upper punch 32 is extended downward by the operation of the upper molding device 30, and at the same time the lower molding device 31 is moved. By the operation, the lower punch 33 extends upward, so that the upper punch 32
The raw material a is compression-molded between the lower end of the base and the upper end of the lower punch 33 to produce the preparation a ′. In this case, if the upper punch 32 and the lower punch 33, which are parts in contact with the raw material a, are formed of Ti alloy or the like, or if the surface is coated with diamond-like C or the like, the upper punch 32 and the lower punch 33 are It is possible to prevent corrosion by the raw material a.

Next, the formulation a'manufactured (compressed and molded) in the mortar 15 at the station C in this way is sequentially held in the mortar 15 and sequentially transferred to the station D as the first table 11 is intermittently rotated. Moving. Also in this case, if the die 15 that is a part in contact with the formulation a ′ (raw material a) is formed of a Ti alloy or the like, or if the surface is coated with diamond-like C or the like, the formulation a ′ is stationed in this way. It is possible to prevent the mortar 15 from being corroded by the preparation a ′ (raw material a) even while moving from C to the station D. In addition, during the movement from the station C to the station D, similarly, the formulation a ′ is prevented from dropping from the die 15.

Thus, the mortar 15 successively passes through the drying device 35 arranged in the station D, and the formulation a'produced (compressed and molded) in the mortar 15 in the above-mentioned station C is held in the mortar 15. Can be dried as it is.

The formulation a'dried by passing through the station D in this way, while being held in the mortar 15, moves to the station E sequentially with the intermittent rotation of the first table 11. Then, as described above with reference to FIG. 9, the take-out device 40 is operated to extend the take-out pin 42 downward, so that the lower end of the take-out pin 42 descends in the mortar 15 and is retained in the mortar 15 until now. The prepared formulation a ′ drops from the mortar 15 and is transferred onto the upper surface of the starting end of the conveyor 41, and is sequentially transported to the outside of the formulation molding apparatus 1. Also in this case, whether the take-out pin 42, which is a part in contact with the formulation a ′ (raw material a), is made of Ti alloy or the like,
Alternatively, if the surface is coated with diamond-like C or the like, the take-out pin 42 can be prevented from being corroded by the preparation a ′ (raw material a).

According to this formulation molding apparatus 1, the hopper 20, which is a part in contact with the raw material a, the fixed quantity container 16 provided on the second table 12, and the filling pin 2 of the filling pressurizing device 25.
6, at least one of the die 15 provided on the first table 11, the upper punch 32 of the upper molding device 30 and the lower punch 33 of the lower molding device 31, and the ejection pin 42 of the ejection device 40 is made of Ti.
It is made of alloy or diamond-like C
Since the surface is coated with etc., it is possible to prevent the respective parts from being corroded by the raw material a.

Although an example of the preferred embodiment of the present invention has been described above, the present invention is not limited to the embodiment exemplified here. For example, the hopper 20, the fixed quantity container 16, the filling pin 26, the die 15, the upper punch 32, the lower punch 33, and the take-out pin 42.
The whole may be formed of a Ti alloy or the like, but only the portion in contact with the raw material a may be formed of a Ti alloy or the surface may be coated with diamond-like C or the like. For example, regarding the filling pin 26, the upper punch 32, and the take-out pin 42, as shown in FIG.
If a coating layer 50 of Ti alloy or the like is formed on the lower end surfaces of the upper punch 32 and the take-out pin 42, the filling pin 26 and the upper punch 32
The entire take-out pin 42 does not have to be formed of a Ti alloy or the like. Further, for example, referring to the lower punch 33, as shown in FIG.
As shown in FIG. 3, if a coating layer 51 of Ti alloy or the like is formed on the upper end surface of the lower punch 33, or if the surface is coated with diamond-like C or the like, the entire lower punch 33 does not have to be formed of Ti alloy or the like. Is also good. Further, for example, the mortar 15 and the fixed quantity container 1
As for 6, the first table 11 and the second table 1
Although the whole 2 may be formed of a Ti alloy or the like, as shown in FIG. 12, a coating layer 52 of a Ti alloy or the like is formed on the inner surface of the die 15 and the fixed quantity container 16, or a diamond-shaped C surface is used. If coated, the first table 11 and the second table
The entire table 12 may not be formed of Ti alloy or the like. Although not shown, the inner surface of the hopper 20 is made of Ti.
If the surface of the hopper 20 is coated with an alloy or the like, or the surface thereof is coated with a diamond-like C or the like, the entire hopper 20 does not have to be formed of a Ti alloy or the like. Corrosion of each component by the raw material a is also effective by coating only the contact point of the raw material a with the Ti alloy or the surface of the diamond-like C or the like in each component contacting with the raw material a. Will be able to prevent.

The mortar 1 formed on the first table 11
5 and the fixed quantity container 1 formed on the second table 12
The number of 6 is arbitrary and is not limited to the number illustrated in the embodiment. For example, on the first table 11, 6 in the circumferential direction.
2 pieces × 4 rows of mortars 15 are provided at equally divided positions, or 4 pieces × 8 rows of mortars 15 are provided at equally divided positions in the circumferential direction.
The location and the number of mortars 15 to be disposed are arbitrary, for example, each of them is provided. Similarly, the location and number of the fixed quantity containers 16 formed on the second table 12 are arbitrary. Further, the present invention is disclosed in, for example, Japanese Patent Application Laid-Open Nos. 8-19588 and 8-1.
No. 9589, Japanese Patent Laid-Open No. 8-19590, etc.
It can also be applied to a device for tableting through a film.

[0041]

[Examples] With respect to the materials constituting the parts of the apparatus for molding the preparation of the present invention, the corrosion resistance to corrosive substances was examined.

(Example 1) Influence of corrosive drug exposure (part 1) With respect to the materials of Comparative Examples, SUS304, SUS316, and SUS420JK were examined for corrosion resistance to drugs. Further, as materials for the examples of the present invention, pure titanium (DAT-1: trade name, Daido Steel Co., Ltd.), titanium alloy (DAT-5E: trade name, composition: Ti-6AL).
-4V, Daido Steel Co., Ltd., MAT-21 (trade name, Mitsubishi Materials, Ni-19Cr-19Mo-1.8Ta), Hastelloy B2 (trade name,
MITSUBISHI MATERIALS CORPORATION, Ni-Mo alloy, ULTIMATE ALLOY (trade name, MITSUBISHI MATERIALS CORPORATION, Co base alloy, 9Ni-3Fe-
26Cr-5Mo) was examined for corrosion resistance to drugs.
Furthermore, the corrosion resistance to the drug was examined for each of the base material (SUS316) treated with hard chromium (Cr), nickel (Ni) or tantalum (Ta) amorphous.

Test pieces made of the above materials (plate thickness
About 3 g each of donepezil hydrochloride, enalapril maleate, meclizine hydrochloride, scopolamine hydrobromide, or oxybutynin hydrochloride was applied to a plate (3 mm x 50 mm x 25 mm wide, 5 mm diameter hole at the top). Thereafter, 0.3 g of a 50% ethanol aqueous solution was added dropwise to the drug-coated portion, and 2 hours later, similarly, 0.3 g of a 50% ethanol aqueous solution was added dropwise. Two hours later, each test piece was washed with purified water, and the change of the surface was visually confirmed. The results are shown in Table 1.
Shown in.

[0044]

[Table 1]

As is clear from Table 1, pure titanium, titanium alloy, MAT-21, ultimate alloy, tantalum amorphous and hard Cr-treated ones have the best corrosion resistance.
Next, Hastelloy B2 and Ni treated products were excellent.

Example 2 Measurement of Corrosion Rate 110 g of 25% ethanol aqueous solution was placed in a plastic container,
14.5 g of meclizine hydrochloride was added to make a saturated aqueous solution.
As an example, MAT-21, Hastelloy B2, Ultimate Alloy, pure titanium and titanium alloy (Ti-6Al) were added to this solution.
-4V test piece and, as a comparative example, SUS304 and SUS316 test pieces (each test piece is 3 mm thick × 50 mm long × horizontal
25mm, a plate with a 5mm diameter hole on top)
It was stored in a closed manner at ℃ for 1 month.

After one month, each test piece was washed with ethanol, the corrosion rate of each test piece was calculated using the following equation (1), and the corrosion rate of MAT-21 was set to 1. The relative corrosion rates of other test pieces were calculated, and the corrosiveness to meclizine hydrochloride was evaluated (Tables 2 and 3).

Formula (1): Corrosion rate (mm / year) = [87.60 × corrosion weight loss (mg)] /
[Surface area of the steel Density (g / cm ³⁾ × test piece (cm ²⁾ × test time (hr)]

[0049]

[Table 2]

[0050]

[Table 3]

The corrosion rates of pure titanium, titanium alloy, MAT-21 and ultimate alloy were very slow, and the materials had excellent corrosion resistance.

Example 3 A tableting turntable having a die was prepared using pure titanium and MAT-21. Sliding a wet powder containing the acidic drug meclizine hydrochloride and scopolamine hydrobromide (the formulation of which is shown in Table 4), the turntable corrosion conditions of 0.5, 1, 2,
It was visually confirmed after 3, 4, 5 and 6 hours. As a result, no corrosion or deterioration was found on the turntables of any material.

[0053]

[Table 4]

(Example 4) Influence of exposure to corrosive agents (Part 2) Using SUS420J2 as a base material, this surface was treated with tantalum amorphous, Nifgrip (trademark, Alpac Techno Co., Ltd.) treatment, diamond-like C coating (Diamond like carbon coat
ing, DLC), titanium coating, titanium-titanium nitride coating (Ti-titanium nitride double coating), Celtes N (trade name, Nanocoat TS Co., Ltd., chrome nitride coating), chrome dope-
With respect to the N-treated product, the adhesion of wet powder of acidic drug and the corrosion resistance to exposure to acidic drug were examined.

(1) The above-mentioned surface treatment was applied to the die for molding the adhesive solid preparation and the preparation take-out pin, and the same wet powder as in Example 3 was used.
A quick-disintegrating tablet was manufactured. As a result, the DLC, titanium, and titanium-titanium nitride coatings showed almost no adhesion of wet powder. In addition, in the case of Nif Grip and those treated with Ta amorphous, slight adhesion of powder was observed (Table 5).

(2) Corrosion resistance A test piece (thickness: 3 mm × length: 50 m) subjected to the above surface treatment.
m × width 25 mm) is dipped in a meclizine hydrochloride suspension with a 50% (V / V) ethanol aqueous solution, and it is kept at 40 ° C. for 3 days.
After storage for one day, peeling and corrosion of the coating were observed. As a result, DLC, titanium, titanium-titanium nitride coating and Celtes N showed no change on the surface of the test piece. In addition, a slight corrosion was observed in the untreated and Ta-amorphized ones. With Nif Grip treatment and Chrome Dope-N treatment,
The coating was peeled off.

[0057]

[Table 5]

[0058]

INDUSTRIAL APPLICABILITY According to the present invention, a corrosive raw material such as a tablet containing an acidic substance such as donepezil hydrochloride, enalapril maleate, meclizine hydrochloride, scopolamine hydrobromide, and oxybutynin hydrochloride is compression molded. Thus, when molding the drug product, the corrosion resistance of the parts of the drug product molding device can be further improved. This formulation molding device does not require special maintenance and can reduce labor. Further, it is possible to stably manufacture a preparation of the same quality over a long period of time.

[Brief description of drawings]

FIG. 1 is a plan view of a formulation molding apparatus according to an embodiment of the present invention.

FIG. 2 is a front view of the formulation molding apparatus as viewed from below in FIG.

FIG. 3 is a right side view of the formulation molding apparatus as viewed from the right in FIG.

FIG. 4 is an explanatory diagram showing a state in which a filling pin is located right above a fixed quantity container and a mortar that are positioned and stopped at station B.

FIG. 5 is an explanatory view showing a state in which the filling pin is lowered and the raw material filled in the fixed quantity container is pushed down into the die.

FIG. 6 is an explanatory view showing a state in which an upper punch and a lower punch are located above and below a die which is positioned and stopped at a station C;

FIG. 7 is an explanatory view showing a state in which a raw material is compression-molded between an upper punch and a lower punch to produce a preparation in a die.

FIG. 8 is an explanatory diagram showing a state in which a take-out pin is positioned just above a die which is positioned at a station E and stopped.

FIG. 9 is an explanatory diagram showing a state in which the take-out pin is lowered, the preparation drops from the die, and is transferred onto the upper surface of the conveyor.

FIG. 10 shows T on the lower end surfaces of the filling pin, the upper punch and the take-out pin.
It is a partially enlarged view of an embodiment in which a coating layer such as an i alloy is formed.

FIG. 11 is a partially enlarged view of an embodiment in which a coating layer such as a Ti alloy is formed on the upper end surface of the lower punch.

FIG. 12 is a partially enlarged view of an embodiment in which a coating layer of Ti alloy or the like is formed on the inner surfaces of a die and a metering container.

[Explanation of symbols]

1 Formulation molding equipment a raw material a'preparation 10 Device body 11 First Table 12 Second table 13,14 Rotary drive shaft 15 mortar 16 fixed quantity container 20 hopper 25 Filling pressurizing device 26 Filling pin 30 Upper molding equipment 31 Lower molding equipment 32 Upper punch 33 Lower punch 35 Dryer 40 Take-out device 41 conveyor 42 Takeout pin

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 31/495 A61K 31/495 38/55 A61P 25/00 A61P 25/00 B30B 11/08 A B30B 11 / 08 Z A61K 37/64 (72) Inventor Yuki Tsushima 1-10-27 Kashiwa, Honjo City, Saitama Prefecture (reference) 4C076 AA37 BB01 CC01 FF01 FF36 GG14 4C084 AA03 BA01 BA14 BA23 CA59 MA35 MA52 NA03 ZA012 4C086 AABC BC07 BC BC50 CB05 GA16 MA01 MA04 MA35 MA52 NA03 ZA01 4C206 AA04 FA05 MA01 MA04 MA55 MA72 NA03 ZA01

Claims (17)

[Claims] 1. A component, which is in contact with the raw material in a pharmaceutical molding apparatus for compressing and molding a raw material made of corrosive granules or powders, the raw material being Ti, Ti alloy, or Ni—Cr.
A component of a formulation molding apparatus, which is formed of one or more metals selected from the group consisting of —Mo alloys, Ni—Mo alloys, and Co-based alloys. 2. A component which is in contact with a raw material in a formulation molding apparatus for compressing and molding a raw material composed of corrosive granules or powders, the diamond-shaped C, Ti, titanium nitride, chromium nitride and Ti-- A component of a formulation molding machine, characterized in that the surface is coated with one of the double coats of titanium nitride. 3. The parts include a hopper for storing the raw material, a fixed quantity container for quantitatively transporting the raw material, a die for molding the formulation, a filling pin for filling the die with the raw material, and the formulation. The part of the formulation molding apparatus according to claim 1 or 2, which is one of a punch for molding and a take-out pin for removing the formulation from a die that molds the formulation. 4. A drug product forming apparatus for forming a drug product by compression molding a raw material made of corrosive granules or powders, wherein a hopper for storing the raw material and a die for molding the drug product are formed. A first table, a filling pin for filling the mortar with the raw material stored in the hopper in fixed amounts, a punch for compressing the raw material with which the mortar is filled to mold the formulation, and the formulation from the mortar A take-out pin for taking out, at least one of the hopper, the die, the filling pin, the punch, and the take-out pin is T
A formulation molding apparatus characterized by being formed of one or more metals selected from the group consisting of i, Ti alloys, Ni-Cr-Mo alloys, Ni-Mo alloys and Co-based alloys. 5. A formulation molding apparatus for molding a formulation by compression-molding a raw material composed of corrosive granules or powder, comprising a hopper for storing the raw material and a die for molding the formulation. A first table, a filling pin for filling the mortar with the raw material stored in the hopper in fixed amounts, a punch for compressing the raw material with which the mortar is filled to mold the formulation, and the formulation from the mortar And a take-out pin for taking out, wherein at least one of the hopper, the die, the filling pin, the punch and the take-out pin is diamond-like C, Ti, titanium nitride, chromium nitride and T.
An i-titanium nitride double coating, the surface of which is coated. 6. The formulation forming apparatus according to claim 4, further comprising a second table formed with a fixed amount container that conveys the raw materials accumulated in the hopper in fixed amounts. 7. The quantitative container comprises Ti, Ti alloy, Ni
The formulation molding apparatus according to claim 6, which is formed of at least one metal selected from the group consisting of a -Cr-Mo alloy, a Ni-Mo alloy, and a Co alloy. 8. The quantitative container is diamond-shaped C, T
7. The preparation molding apparatus according to claim 6, wherein the surface is coated with any one of i, titanium nitride, chromium nitride, and Ti-titanium nitride double coating. 9. A method for compressing and molding a raw material made of corrosive granules or powders by the formulation molding apparatus according to claim 4, 5, 6, 7 or 8 to mold the raw material. And a step of compressing the raw material with which the die is filled to form the formulation, and a step of removing the formulation from the die. 10. The molding method according to claim 9, wherein the raw material contains an acidic drug and a salt thereof, an inorganic acid salt of a basic drug or an organic acid salt of a basic drug. 11. The acidic drug and salts thereof are ascorbic acid, calcium ascorbate, nicotinic acid,
The molding method according to claim 10, which is any one of salicylic acid, acetylsalicylic acid, sodium valproate, sodium azulenesulfonate, and sodium diclofenac. 12. The inorganic acid salt of a basic drug comprises thiamine hydrochloride, riboflavic acid phosphate, pyridoxine hydrochloride, pyridoxal phosphate, pyridoxal hydrochloride, meclizine hydrochloride, scopolamine hydrobromide, methylephedrine hydrochloride, dihydrocodeine phosphate, Ranitidine hydrochloride, berberine chloride, etilefrine hydrochloride, fursultiamine hydrochloride,
Loperamide Hydrochloride, Donepezil Hydrochloride, Oxybutynin Hydrochloride, Propiverine Hydrochloride, Nicardipine Hydrochloride, Manidipine Hydrochloride, Benidipine Hydrochloride, Diphenidol Hydrochloride, Diphenylpyraline Hydrochloride, Diphenhydramine Hydrochloride, Promethazine Hydrochloride, Oxyphencycline Hydrochloride, Dicyclomine Hydrochloride, Methixene Hydrochloride, Methylatropine Hydrochloride, The molding method according to claim 10 or 11, which is one of papaverine hydrochloride, loperamide hydrochloride, and cetirizine hydrochloride. 13. The organic acid salt of the basic drug is any one of chlorpheniramine maleate, enalapril maleate, diphenhydramine salicylate, ergotamine tartrate, bromocributine mesylate, amethinium methyl sulfate, ketotifen fumarate, and fluvoxamine maleate. The molding method according to claim 10, 11 or 12, which is 14. The molding method according to claim 9, 10, 11, 12 or 13, wherein the preparation is a mold tablet. 15. A formulation formed by using the formulation forming apparatus according to claim 4, 5, 6, 7 or 8. 16. A pharmaceutical composition molded by the molding method according to claim 9, 10, 11, 12, 13 or 14. 17. The preparation according to claim 15 or 16, wherein the preparation is a mold tablet.