JPH10192370A - Production of capsule agent and apparatus for production of the capsule agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a process for producing capsule agents which is capable of packing these capsule agent into capsules without the occurrence of sticking. SOLUTION: A prescribed amt. of powder and granular materials are taken out and the prescribed amt. of the taken out powder and granular Materials are packed into the bodies Ca of the capsules by using a capsule packing device 2 which is coated with lubricants in contact parts S2a, S2b by applying the lubricant on the contact parts S2a, S2b where the powder and granular materials of the capsule packing device 2 come into contact under the state in which the lubricants are diffused by air pulsation waves.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing capsules and an apparatus for producing capsules, and more particularly, to a method in which a granular material to be filled in a capsule adheres to a capsule filling machine (also referred to as sticking). The present invention relates to a capsule manufacturing method and a capsule manufacturing apparatus which can be filled in a capsule without using the same.

[0002]

2. Description of the Related Art Conventionally, in a method for producing capsules, FIG.
In the process shown in FIG. 9A, an inner peripheral surface S102a which is a contact portion of the funnel 102a of the capsule filling device 102 shown in FIG. Plunger 102b
Lower end surface S102b which is a contact portion that comes into contact with the granular material
The main drug (active ingredient) or the solid drug (powder, granule, etc.) is used to prevent the powder material from adhering to the capsule and to improve the fluidity of the powder material. In addition to excipients and disintegrants added as needed, a lubricant such as magnesium stearate, sodium lauryl sulfate, talc, etc. is added in an amount of about 0.1% by weight or more to the granular material. 5% by weight or less and uniformly mixed using a mixer 110.
In the step shown in (b), a predetermined amount of the granular material M stored in the granular material storage tank 103 is taken out using the capsule filling device 102 (see FIG. 9 (c)) and taken out. A predetermined amount of the granular material m is filled into the body Ca of the capsule fixed in the capsule fixing hole h104 of the dispensing table 104, and the body C filled with the predetermined amount of the granular material m
a, cap Cb of the capsule is sealed, and a capsule Cd
Is manufactured (see FIG. 9D).

In this example, a method of manufacturing a press-type capsule agent having a funnel 102a and a plunger 102b movably provided in the funnel 102a has been described as an example of the capsule filling device 102.
Auger type, disk type, even when using a compressed capsule filler, in order to prevent the particulate material from adhering to the contact portion that contacts the particulate material, in the particulate material, A lubricant is uniformly mixed in advance (in the present specification, a method of manufacturing a capsule in which a lubricant is uniformly mixed in advance in a powder material is referred to as an internal lubrication method. ).

[0004]

However, according to the internal lubrication method described above, for example, when the granular material is a drug having strong sticking properties, capping properties, and lamination properties such as ascorbic acid, acetaminophen, amoxicillin and the like. However, there has been a problem that the particulate material adheres to a contact portion of the capsule filling device which comes into contact with the particulate material, and it becomes impossible to continuously fill the capsule with the particulate material. When the granular material adheres to the contact portion of the capsule filling device that comes into contact with the granular material, conventionally, countermeasures such as increasing the amount of a lubricant to be added to the granular material have been tried. Because of the strong sticking property of some drugs, such countermeasures still cause the particulate material to adhere to the contact portion of the capsule filler that comes into contact with the particulate material. There are drugs that need to be abandoned.

[0005] In recent years, capsules include, in addition to ordinary capsules, fast-dissolving capsules, sustained-release capsules, enteric-coated capsules, large intestine disintegrating capsules, gastric floating capsules, intestinal adhesive capsules, oral quick-dissolving capsules, oral adhesives Capsule, sustained release capsule in oral cavity, multi-layer capsule, multi-granule-containing capsule, effervescent capsule, capsule taken by dissolving in water,
Capsules for gargle and oral cleansing, vaginal and rectal capsules, implantable capsules,
Capsules used for in-vivo diagnosis and external diagnosis, capsules not only for medical use but also for various purposes, and products in the form of capsules are widely used. Also, the content of the capsule is desired to have the property of dissolving at the target site. However, when the amount of the lubricant in the granular material is increased, a large amount of the lubricant is included in the contents of the capsule. And since the lubricant usually has water repellency, due to the water repellency of the lubricant, the disintegration time of the contents of the capsule, or the dissolution time is extended, and the content of the contents over time There is a problem that the physical properties change, the quality of the added lubricant and the mixing state, the physical properties of the contents change over time, etc., and at a predetermined site, the contents do not collapse. There is a problem that the capsule does not dissolve or dissolve, and the performance of the capsule cannot be sufficiently exhibited.

A first object of the present invention is to solve the above problems. For example, a drug (powder material) filled in a capsule has a strong sticking property. Even if it is, the powder material can be filled into the capsule without adhering to the contact portion of the capsule filling device that comes into contact with the powder material, and furthermore, the content of the capsule to be produced can be It is an object of the present invention to provide a capsule manufacturing method and a capsule manufacturing apparatus which, when melted, rapidly melt the contents of the capsule at the site.

[0007] Some of the capsules have been carefully designed in consideration of the properties of the lubricant at the design stage, and product evaluations have been established after many years of administration, and the disintegration of the capsule contents has been established. It is not desirable to change the properties and dissolution characteristics of capsules, but on the other hand, in the process of manufacturing capsules, in order to further increase the production efficiency of capsules, it comes into contact with the granular material of the capsule filler. There is also a demand for further reducing adhesion of the granular material to the contact portion.

A second object of the present invention is to solve the above-mentioned problems, and it is possible to improve the disintegration and dissolution characteristics of the contents of the capsule without changing the powder of the capsule filling device. An object of the present invention is to provide a capsule manufacturing method and a capsule manufacturing apparatus, which further reduce the adhesion of the granular material to a contact portion that comes into contact with the granular material.

[0009]

Means for Solving the Problems The present inventors have studied for a long time a method and an apparatus for solving the above problems, and as a result of considering the function of the lubricant, the lubricant is: It has been found that if there is a trace amount between the mold of the capsule filling device and the molded product molded by the mold, the function should be sufficiently fulfilled. -11273, JP-A-56-1409
No. 8, there is a so-called external lubrication method for producing tablets, and it has been concluded that these techniques may be applied to a method for producing capsules.

FIG. 10 is a process diagram schematically showing a method for producing a tablet described in Japanese Patent Publication No. 41-11273. In the tablet manufacturing method, first, in the step shown in FIG. 10A, the lubricant injection nozzle 206 slides the lower end surface S203 of the upper punch 203 and the upper end surface S205 of the lower punch 205 side. The powder K is sprayed and sprayed by air pressure, and in the step shown in FIG. 10B, the molding material m is filled in the die 202 of the dispensing table 204 which is rotatably provided. In the process shown, the molding material m
Is compression-molded with both an upper punch 203 having a surface coated with a lubricant K and a lower punch 205 having a surface coated with a lubricant K to produce tablets.

FIG. 11 is a graph showing the characteristics of Japanese Patent Application Laid-Open No. 56-14098.
BRIEF DESCRIPTION OF THE DRAWINGS FIG. In this tablet manufacturing method, first, FIG.
In the step shown in (a), a spraying chamber 2 provided above a mill 202 at a predetermined position of a dispensing table 204 rotatably provided.
07a was sprayed with lubricant K.
As shown in (b), the lower punch 205 is placed on the upper end surface S205. Thereafter, in the step shown in FIG. 11C, the lower punch 205 is moved from the nozzle 208 arranged in the spray chamber 207b.
By injecting compressed air into the lower punch 205
The upper lubricant K is blown up and separated, and the separated lubricant is applied to the inner peripheral surface S202 of the die 202 or the upper punch 20.
3 is attached to the lower end surface S203, and thereafter, the mill 202
The inner peripheral surface S202, the lower end surface S203 of the upper punch 203, and the upper end surface S205 of the lower punch 205 are coated with a lubricant K, and are formed using a die 202, an upper punch 203, and a lower punch 205. The material is compression molded to produce tablets.

However, the above-mentioned Japanese Patent Publication No. Sho 41-11
273 and JP-A-56-14098, in any case, the inner peripheral surface S202 of the die 202 and the lower end surface S of the upper punch 203 during a long tableting operation.
Since the lubricant K cannot be stably and uniformly applied to the upper surface 203 of the lower punch 205 and the lower punch 205, such a tablet manufacturing method is an industrial tablet manufacturing method. There is a problem that can not be implemented as.

Therefore, the present inventors, when applying these techniques to a method for producing capsules, contact the lubricant uniformly and stably with the powder material of the capsule filler. As a result of diligent research into the technology of applying to the contact area, the use of air pulsation waves has shown that the lubricant can be stably and uniformly applied to the contact area where the granular material of the capsule filler comes into contact. As a result of finding out what can be done and working diligently, the present invention has been completed.

[0014] That is, according to the method for producing a capsule according to the first aspect, a capsule is produced by filling a predetermined amount of the granular material in a capsule by using a capsule filling device. In a state in which the lubricant is diffused by the air pulsating wave, the lubricant is applied to the contact portion of the capsule filling device where the powder material contacts, and the capsule filling in which the lubricant is applied to the contact portion Using a container, a predetermined amount of the granular material was taken out, and the taken-out predetermined amount of the granular material was filled in the capsule.

The capsule filling device may be any of a press type, an auger type, a disk type and a compressed type.
Here, the “contact portion of the capsule filler where the powder and granular material comes into contact” is, for example, in the case of a press type, an inner peripheral surface that is a contact portion that contacts the powder and granular material of the funnel, and In the case of the auger type, the inner peripheral surface of a storage tank for storing the granular material to be filled in the capsule, which means a lower end surface that is a contact portion that comes into contact with the granular material of the plunger movably provided. Means the inner peripheral surface of the spiral-shaped cutting surface and the nozzle provided at the lower part of the storage tank. In the case of the disk type, the inner peripheral surface of the storage tank for storing the granular material to be filled in the capsule. And the inner peripheral surface of the nozzle provided at the lower part of the storage tank, and in the case of the compression type, the surface of the compression plunger.

The air pulsation wave may be an air pulsation wave in a pressurized atmosphere or an air pulsation wave in a suction atmosphere as long as the lubricant can be sufficiently diffused. According to a second aspect of the present invention, there is provided a method for producing a capsule, wherein the air pulsation wave of the method for producing a capsule according to the first aspect is an air pulsation wave in a pressurized atmosphere. The air pulsation wave of the pressurized atmosphere has a positive amplitude at the peak of the amplitude and an atmospheric pressure at the valley, and both the peak and the valley of the amplitude have the positive pressure even if these are alternating air pulsation waves. It may be an air pulsation wave. However, in general, the energy loss when pneumatically transporting the granular material is considered to be the resistance between the granular material and the conduit,
It is preferable to use an air pulsation wave in which both peaks and valleys of the amplitude are positive pressure.

This is because, when the peaks of the amplitude are positive pressure and the valleys are the atmospheric pressure, and these use the air pulsation wave which appears alternately,
Lubricants that are pneumatically transported alternately move and stop in the conduit, requiring a lot of energy to move the stopped lubricant again,
If the peaks and valleys of amplitude use air pulsation waves that are both positive pressure, the lubricant that is pneumatically transported will repeatedly move fast and slowly in the conduit, This is because the lubricant that is pneumatically transported always moves, so that the energy for moving the lubricant can be reduced by the amount that the static friction coefficient does not matter.

According to a third aspect of the present invention, there is provided a method for producing a capsule, wherein the air pulsation wave in the method for producing a capsule according to the first aspect is an air pulsation wave of a suction atmosphere. The air pulsation wave of the suction atmosphere has the amplitude peak at atmospheric pressure and the valley at negative pressure, even if these are alternating air pulsation waves.
The peaks and valleys of the amplitude may be air pulsation waves that are both negative pressures. However, in general, the energy loss during the pneumatic transport of the granular material is considered to be a negative pressure when both the peaks and valleys of the amplitude are considered to be the resistance between the granular material and the conduit. It is more preferable to use the air pulsation wave.

This is because when the peaks of the amplitude are at atmospheric pressure and the valleys are at negative pressure, and they use air pulsation waves that appear alternately,
Lubricants that are pneumatically transported alternately stop and move in the conduit, requiring a lot of energy to move the stopped lubricant again,
If the peaks and valleys of amplitude use air pulsation waves that are both negative pressure, the lubricant that is pneumatically transported will repeat slow and fast movement in the conduit, and Since the lubricant which is pneumatically transported always moves, it is considered that the energy for moving the lubricant can be reduced by the amount that the static friction coefficient does not matter.

[0020] The method for producing a capsule according to claim 4 specifically specifies the amount of the lubricant contained in the capsule to be produced, and the capsule according to any one of claims 1 to 3. The amount of the lubricant applied to the contact portion of the capsule filling device of the method for producing a capsule in which the particulate material contacts is 0.0001% by weight or more and 0.2% by weight or less of the total weight of the capsule to be produced. Preferably, the content is 0.0001% by weight or more and 0.1% by weight or less.

In the capsules produced by this production method, when no lubricant is added to the granular material used, a small amount of lubricant adheres to the surface of the contents of the capsules. However, since the lubricant is not contained inside the content, the disintegration time and dissolution time of the content are not delayed due to the water repellency of the lubricant. In the method for producing a capsule according to the fifth aspect, a lubricant is not added to a predetermined amount of the granular material in the method for producing a capsule according to any one of the first to fourth aspects.

According to the present invention, even when the amount of the lubricant is set to 0.0001% by weight or more and 0.1% by weight or less of the total weight of the capsule to be produced, the contact of the granular material of the capsule filling device with the lubricant can be achieved. The particulate material does not adhere to the portion, and the particulate material filled in the capsule does not cause sticking or the like. Also, Japanese Patent Publication No. 41-11273 and Japanese Patent Application Laid-Open
In the method for producing tablets described in JP-A-6-14098,
Since almost no lubricant is contained inside the tablet, the disintegration rate and dissolution rate are increased compared to tablets manufactured by the usual internal lubrication method, and the physical properties of the tablet are changed. There is a problem.

[0023] The method for producing a capsule according to claim 6 is proposed to solve such a problem, and a predetermined amount of the method for producing a capsule according to any one of claims 1 to 4 is provided. A predetermined amount of lubricant is added to the granular material of the present invention, and a predetermined amount of lubricant contained in the granular material is in contact with the granular material of the capsule filler. And the total amount of the lubricant applied to the lubricant is adjusted to the weight of the lubricant used in the internal lubricant method.

Since the amount of the lubricant contained in the content of the capsule prepared by this method for producing a capsule is adjusted to the weight of the lubricant used in the internal lubrication method, the content of the content of the lubricant is adjusted. Physical properties of capsules produced by the internal lubrication method are not much different from those of the capsule contents. In addition, a part of the amount of the lubricant used in the internal lubrication method is used, and the air pulsation wave is used to apply the powder material to the contact portion of the capsule filling device where the powder material is in contact. Compared with the internal lubrication method, the granular material does not adhere to the surface of the contact portion of the capsule filling device where the granular material contacts.

An apparatus for producing a capsule according to a seventh aspect of the present invention proposes an apparatus for producing a capsule which generates an air pulsation wave in a pressurized atmosphere. A powder filling material storage tank, a dispensing table for fixing the capsule body, and a capsule filling device provided for filling a predetermined amount of the powder and granular material into the capsule body fixed to the dispensing table. And a lubricant spraying chamber that is provided for applying a lubricant to a contact portion of the capsule filler where the powder material contacts, and temporarily stores the contact portion of the capsule filler where the powder material contacts. Air pulsation wave generating means connected to the lubricant spraying chamber via a conduit, air supply means connected upstream of the air pulsation wave generating means, and air pulsation wave generating means connected to the conduit A lubricant storage tank connected to the downstream side The air supply means and the air pulsation wave generating means are driven to generate an air pulsation wave of a pressurized atmosphere in the conduit and the lubricant spraying chamber, and the lubricant storage tank is generated by the air pulsation wave of the pressurized atmosphere. The lubricant contained therein is diffused into the lubricant spraying chamber, and the contact portion of the capsule filling device that contacts the granular material is accommodated in the lubricant spraying chamber,
A lubricant is applied to the surface of the contact portion of the capsule filling device that contacts the granular material, and the powder is applied using the capsule filling device in which the lubricant is applied to the surface of the contact portion that contacts the granular material. Take out a predetermined amount of the granular material stored in the granular material storage tank,
A predetermined amount of the granular material taken out was filled into the body of the capsule fixed to the dispensing table.

The air pulsation wave generating means is constituted by an open / close control valve or the like provided on the downstream side of the air supply means of the conduit.
An apparatus for manufacturing a capsule according to claim 8 proposes an apparatus for manufacturing a capsule which generates an air pulsation wave in a pressurized atmosphere in which both peaks and valleys of amplitude are positive pressure. Item 7. The air pulsating wave generating means of the capsule manufacturing apparatus according to Item 7, wherein a cylindrical case body having a pair of connection ports on a peripheral wall surface, and a center axis of the cylindrical case body as a rotation axis, and the inside of the case body. A rotary valve provided so as to be divided, one of a pair of connection ports provided on the peripheral wall is connected to the air supply means, and the other is connected to one end of the conduit.

An apparatus for manufacturing a capsule according to a ninth aspect of the present invention proposes an apparatus for manufacturing a capsule which generates an air pulsating wave in a suction atmosphere, and stores a granular material to be filled in the capsule. A powder material storage tank to be filled, a dispensing table for fixing the capsule body, and a capsule filling device provided to fill a predetermined amount of the powder material to the capsule body fixed to the dispensing table. A lubricant spraying chamber that is provided to apply a lubricant to a contact portion of the capsule filler where the powder material contacts, and temporarily stores the contact portion of the capsule filler where the powder material contacts, Lubricant spraying means for spraying a lubricant into the lubricant spraying chamber, air pulsation wave generating means provided to be connected to the lubricant spraying chamber, and provided on the downstream side of the air pulsating wave generating means Air suction hand to suck the air in the lubricant spraying room And spraying the lubricant from the lubricant spraying means into the lubricant spraying chamber, and driving the air suction means and the air pulsation wave generating means to generate air pulsation waves in the lubricant spraying chamber. The lubricant sprayed from the lubricant spraying means into the lubricant spraying chamber is diffused into the lubricant spraying chamber, and the contact portion of the capsule filling device, which comes into contact with the granular material, is formed in the lubricant spraying chamber. The lubricant is applied to the surface of the contact portion in contact with the granular material, and the lubricant is applied to the surface of the contact portion in contact with the granular material. A predetermined amount of the granular material stored in the granular material storage tank was taken out, and the taken-out predetermined amount of the granular material was filled into the body of the capsule fixed to the dispensing table.

Here, the air pulsation wave generating means is constituted by an opening / closing control valve and the like provided on the upstream side of the air suction means of the conduit. An apparatus for producing a capsule according to claim 10,
An air pulsation wave generating means of the capsule manufacturing apparatus according to claim 9, which proposes a capsule manufacturing apparatus in which peaks and valleys of amplitude generate air pulsating waves both of which are negative pressure. Is provided with a cylindrical case body having a pair of connection ports on a peripheral wall surface, and a rotary valve provided so as to divide the case body around a center axis of the cylindrical case body as a rotation axis. One of the pair of connection ports provided is connected to the air suction means, and the other is connected to the lubricant spraying chamber.

[0029]

BEST MODE FOR CARRYING OUT THE INVENTION

(Embodiment 1) In this example, an apparatus for producing a capsule which generates an air pulsation wave in a pressurized atmosphere will be described. FIG. 1 is an overall configuration diagram schematically showing a capsule manufacturing apparatus according to the present invention.

The capsule manufacturing apparatus 1 includes a powder material storage tank 3 for storing the powder material to be filled in the capsule.
A dispensing table 4 for fixing the body Ca of the capsule, a capsule filling device 2 provided for filling a predetermined amount of the granular material m into the body Ca of the capsule fixed on the dispensing table 4, The lubricant spraying chamber 5 and the lubricant spraying chamber 5 are connected to the conduit 6
Pulsating wave generator 7 connected through the air, an air supply device (air supply blower) 8 connected upstream of the air pulsating wave generator 7, and lubricant K are stored. A lubricant storage tank 9;

In this example, a press-type capsule filler 2 having a funnel 2a having a cylindrical shape and a plunger 2b movably provided in the funnel 2a is used. Further, the dispensing table 4 has a disk shape, and a rotation shaft 4ax is provided at the center thereof, and the dispensing table 4 is rotatable about the rotation axis. The dispensing table 4 fixedly accommodates the body Ca of the capsule. A capsule fixing hole h4 is formed,
Each of the capsule fixing holes h4 has a body Ca of the capsule.
An ejector 4e for taking out the capsule from the capsule fixing hole h4 is provided.

The lubricant spraying chamber 5 has an inlet / outlet 5h of the capsule filling device 2 for accommodating and discharging the capsule filling device 2, and the entrance / exit 5h has an entrance / exit of the capsule filling device 2. And opening and closing for preventing leakage of a pulsating wave of air for dispersing the lubricant K and the lubricant K into the lubricant spraying chamber 5 to be supplied into the lubricant spraying chamber 5 A valve 5a is provided. Further, one end of a lubricant collection pipe 10 is connected to the upper lid 5b of the lubricant spraying chamber 5. The other end of the lubricant collection pipe 10 is connected to a lower part of a lubricant collection tank (hopper) 11, and an upper part of the lubricant collection tank (hopper) 11 is connected via an air suction pipe 12 to the lubricant collection tank (hopper) 11. An air suction device (blower for air suction) 13 is connected. And the outlet 1 of the lubricant collection tank (hopper) 11
The lubricant storage tank 9 is connected to 1h via a lubricant cutout shutter 14.

The conduit 6 has a trumpet-shaped lubricant outlet 6a which is open at the top in the lubricant spraying chamber 5. Further, a lubricant storage tank 9 is connected to the conduit 6 via a lubricant supply pipe 15 at a position downstream of the air pulsation wave generator 7, and lubrication is provided below the lubricant storage tank 9. Agent outlet 9h
Is provided with a lubricant cutout shutter 16.

In FIG. 1, members indicated by 17, 18, and 19 indicate a dust removing filter, and a member indicated by 20 indicates a dust collecting filter. FIG. 2 is a schematic sectional view illustrating the configuration of the air pulsation wave generator 7. The air pulsation wave generator 7 includes a pair of connection ports h7 on the peripheral wall surface S7.
a, a cylindrical case body 7a having a and h7b, and a plate-shaped rotary valve 7b provided so as to divide the inside of the case body 7a around a center axis 7ax of the case body 7a as a rotation axis; A pair of connection ports h7a provided in S7,
One h7a of the h7b is connected to an air supply device (air supply blower) 8, and the other h7b is connected to one end of the conduit 6.

When the air pulsating wave generator 7 is driven, the rotary valve 7b is moved to the center shaft 7a of the case body 7a.
It rotates around x as a rotation axis. When this air pulsation wave generator 7 is used, an air pulsation wave generator 7 is driven by driving an air supply device (air supply blower) 8 to feed a constant amount and a constant flow of air into the conduit 6. When the rotary valve 7b is driven, the air supply device (air supply blower) 8 and the conduit 6 communicate with each other when the rotary valve 7b is in the position shown by the solid line, so that the air supply device (air supply blower) 8 The generated air is sent into the conduit 6.

When the rotary valve 7b is in the position indicated by the imaginary line, the space between the air supply device (air supply blower) 8 and the conduit 6 is shut off by the rotary valve 7b. And, of the two spaces A1 and A2 divided by the rotary valve 7b in the case body 7a, the space connected to one connection port h7a connected to the air supply device (air supply blower) 8. In A1, the air sent from the air supply device (air supply blower) 8 is compressed,
In the space A2 on the side connected to the other connection port h7b connected to the compressed air, compressed air is sent into the conduit 6. Due to the repetition of the rotation of the rotary valve 7b, an air pulsation wave of a pressurized atmosphere in which both peaks and valleys of amplitude pulsate with positive pressure as shown in FIG.
It occurs inside and in the lubricant spraying chamber 5 connected to the conduit 6.

Next, a method for producing a capsule using the capsule production apparatus 1 will be described below with reference to FIGS. First, in the step shown in FIG. 4A, the air supply device (air supply blower) 8 and the air pulsation wave generation device 7 are driven, and the conduit 6 and the lubricant spray chamber 5 are driven.
Inside, an air pulsation wave of a pressurized atmosphere is generated. At substantially the same time, the lubricant cutout shutter 16 of the lubricant storage tank 9 is opened by a predetermined amount. When the air pulsation wave of the pressurized atmosphere flows through the conduit 6, an air flow of a suction atmosphere from the lubricant storage tank 9 toward the conduit 6 is generated in the lubricant supply pipe 15, so that the lubricant storage tank Lubricant K stored in 9
Is supplied into the conduit 6 and is pneumatically transported into the lubricant spraying chamber 5 together with the pulsating air of the pressurized atmosphere flowing through the conduit 6, and the air in the pressurized atmosphere is dispersed in the lubricant spraying chamber 5. The state is diffused by the pulsating wave.

In this example, the air suction device (air suction blower) 13 shown in FIG.
A lubricant recovery tank (hopper) 11
To be collected. By the above operation, the lubricant in the lubricant spraying chamber 5 is stabilized in a state in which the lubricant of a predetermined concentration is diffused. Next, in the step shown in FIG.
The plunger 2b is lifted upward by a predetermined amount, and the capsule filling device 2 having a predetermined capacity formed in the funnel 2a is accommodated in the lubricant spraying chamber 5 through the entrance / exit 5h of the lubricant spraying chamber 5 for a predetermined time, and the air pulsation occurs. Under the condition where the lubricant is diffused by the waves, the contact portion of the capsule filler 2 with which the granular material contacts, that is, the inner peripheral surface S2a of the funnel 2a and the lower end surface S2b of the plunger 2b. Apply a lubricant.

Next, in the step shown in FIG. 4C, the capsule filling device 2 in which the lubricant is applied to the surfaces of the contact portions S2a and S2b with which the granular material comes into contact is removed from the lubricant spraying chamber 5. Take out and in the steps shown in FIGS. 5 (a) and 5 (b)
A contact portion S2 of the capsule filler 1 with which the granular material contacts.
a, A predetermined amount is taken out from the granular material M stored in the granular material storage tank 3 using the capsule filling device 2 in which the lubricant is applied to the surface of S2b, and FIG. ), The lower end of the funnel 2a of the capsule filling device 2 is positioned above the opening of the body Ca of the capsule housed and fixed in the capsule fixing hole h4 of the dispensing table 4, and then the plunger 2b is pushed down. A predetermined amount of the granular material m taken out into the funnel 2a is filled into the body Ca of the capsule (see FIG. 6A).

Next, the cover Cb of the capsule is sealed in the body Ca of the capsule filled with a predetermined amount of the granular material m, and the ejector 4e is projected upward, so that the capsule C
d from the capsule fixing hole h4,
d is manufactured (see FIG. 6B). In the capsule manufacturing apparatus 1, air pulsation waves, more specifically, air pulsation waves in a pressurized atmosphere, and more specifically, both peaks and valleys of amplitude as shown in FIG. Capsule filling device 2 under the condition that lubricant is diffused by air pulsation wave which is pressure
Since the lubricant is applied to the contact portions S2a and S2b where the powder material m is in contact, the lubricant can always be stably and uniformly applied to the contact portions S2a and S2b. This makes it difficult for the particulate material m to adhere to the contact portions S2a and S2b of the capsule filling device 2 where the particulate material m contacts. As a result, even if the drug (granule material) filled in the capsule has a strong sticking property, the contact portions S2a and S2 that come into contact with the granule material of the capsule filling device 2
b) without filling the granular material with the capsule filling device 2
It becomes possible to fill the capsule with the granular material taken out.

Further, according to the method for producing capsules, it is not necessary to add a lubricant to the granular material M stored in the granular material storage tank 3. By merely having a slight amount of a lubricant on the surface of the contents, a capsule containing no or only a very small amount of a lubricant inside the contents can be produced. In addition, capsules containing only a trace amount of lubricant in the contents of the capsules have the problem that the physical properties of the contents change over time due to the water repellency and quality of the lubricant. Is remarkably improved, so that if the capsule dissolves at a predetermined site, the contents will quickly disintegrate or dissolve at the target site, so that the performance of the capsule can be sufficiently exhibited. .

In this example, as the air pulsation wave generator 7, a cylindrical case body 7a having a pair of connection ports h7a and h7b on the peripheral wall surface S7, and a central axis 7 of the case body 7a
and a rotary valve 7b provided to divide the inside of the case body 7a with ax as a rotation axis. One of a pair of connection ports h7a, h7b provided on the peripheral wall surface S7 is connected to the air supply device 8. While the other h7b is shown connected to one end of the conduit 6, the air pulsation wave generator 7 is connected to the conduit 6 as long as the lubricant can be sufficiently diffused in the lubricant spraying chamber 5. Provided on the downstream side of the air supply device 8 of
It may be an open / close control valve.

When an on-off control valve is used, peaks having amplitudes as shown in FIG. 3 (b) are positive pressure, valleys are atmospheric pressure, and the inside of the conduit 6 and the lubricant spraying chamber 5 are shown in FIG. The air pulsation waves of the pressurized atmosphere appear alternately. As the air pulsation wave of the pressurized atmosphere, any of the air pulsation waves shown in FIG. 3A or FIG. 3B can be used, but the peak of the amplitude is positive pressure and the valley is the atmospheric pressure. However, when air pulsation waves that appear alternately are used, the lubricant that is pneumatically transported alternately moves and stops in the conduit, and it is often necessary to move the stopped lubricant again. Where energy is required, peaks and valleys of amplitude, when using air pulsation waves that are both positive pressure, the lubricant that is pneumatically transported,
In the conduit, fast movement and slow movement are repeated, and the lubricant pneumatically transported in the conduit always moves. Therefore, it is considered that the air pulsation wave of the pressurized atmosphere shown in FIG. 3A is more preferable because the energy for moving the air can be reduced.

Hereinafter, the present invention will be described based on specific data. Example 1 1.0% by weight of magnesium stearate was added to a mixture of 36.4% by weight of a furan derivative and 62.6% by weight of corn starch, and mixed for 10 minutes.
A mixed powder for capsule filling was obtained.

As the capsule filling device 2, LZZ manufactured by Xanasi Co., Ltd.
-64 type (made in Italy) was used. Magnesium stearate was used as a lubricant, and pulsating air was used as a transport medium to supply a fixed amount at a mass flow rate of 3.6 g / min.
The lubricant (magnesium stearate) supplied to the lubricant spraying chamber 5 is supplied to an air suction device (a blower for air suction).
By driving No. 13, it was collected, recycled and used.

The amount of the lubricant (magnesium stearate) used for external lubrication was 0.04% of the total weight of the capsule.
The spray amount was adjusted so as to be 03% by weight. The filling speed was 20 capsules per minute. The filling amount of the contents of the capsule was 110 mg, and the contents were filled in No. 4 capsules. Example 2 1.0% by weight of magnesium stearate was added to 99.0% by weight of amoxicillin and mixed for 10 minutes to obtain a mixed powder for filling capsules.

Capsule filling was performed in the same manner as in Example 1 using the capsule preparation apparatus shown in FIGS.
As a lubricant, use magnesium stearate,
Pulsating air was supplied quantitatively at a mass flow rate of 3.6 g / min as a transport medium. The lubricant (magnesium stearate) supplied to the lubricant spraying chamber 5 was collected by driving the air suction means (air blower) 13 and recycled.

The lubricant (magnesium stearate) used for external lubrication was added in an amount of 0.1% of the capsule weight.
The spray amount was adjusted so as to be 03% by weight. The filling speed was 20 capsules per minute. The filling amount of the capsule was 110 mg, which was filled in the No. 4 capsule. (Example 3) Ascorbic acid 10 was obtained by a fluidized-bed granulation method.
The polyvinyl alcohol was sprayed to 100% by weight of the polyvinyl alcohol to 100% by weight of the polyvinyl alcohol to 85% by weight of lactose, and granules were obtained. This granule was prepared in Example 1 using the capsule manufacturing apparatus shown in FIGS. 1 and 2.
Capsule filling was performed in the same manner as described above. The fluidized bed granulator used was WSG15 manufactured by Glatt. The filling amount of the capsule was 110 mg, which was filled in the No. 4 capsule. Comparative Example 1 1.0% by weight of magnesium stearate was added to a mixture of 36.4% by weight of a furan derivative and 62.6% by weight of corn starch, and mixed for 10 minutes.
A mixed powder for capsule filling was obtained.

The capsule is filled in a usual manner without spraying a lubricant, and the filling amount of the capsule is 110 m.
g and filled into No. 4 capsules. (Comparative Example 2) A mixture of 36.4% by weight of a furan derivative and 59.6% by weight of corn starch was mixed with talc 3.0.
% By weight and 1.0% by weight of magnesium stearate were added and mixed for 10 minutes to obtain a mixed powder for capsule filling.

The capsules were filled in a conventional manner without spraying a lubricant, and the filling amount of the capsules was 110 m.
g and filled into No. 4 capsules. Comparative Example 3 2.0% by weight of magnesium stearate was added to a mixture composed of 36.4% by weight of a furan derivative and 61.6% by weight of corn starch, and mixed for 10 minutes to obtain a mixed powder for filling capsules. Was.

The capsules were filled in a usual manner without spraying a lubricant, and the filling amount of the capsules was 110 m.
g and filled into No. 4 capsules. Comparative Example 4 1.0% by weight of magnesium stearate was added to 99.0% by weight of amoxicillin and mixed for 10 minutes to obtain a mixed powder for filling capsules.

The capsule was filled in a usual manner without spraying a lubricant, and the filling amount of the capsule was 110 m.
g and filled into No. 4 capsules. (Comparative Example 5) Ascorbic acid 10 was obtained by a fluidized-bed granulation method.
The polyvinyl alcohol was sprayed on the weight% and lactose 85 weight% to obtain granules, which were sized through a No. 28 wire mesh. These granules were filled and manufactured according to a conventional method without spraying a lubricant.

The fluid bed granulator used was WSG15 manufactured by Glatt. The filling amount of the capsule was 110 mg, which was filled in the No. 4 capsule. Examples 1 to 3 and Comparative Example 1
The filling test results for the samples Nos. To 5 are shown below. Example 1,
In Nos. 2 and 3, sticking did not occur for 40 minutes during the filling test. On the other hand, in Comparative Example 1, sticking occurred in 5 minutes, and production became impossible. In Comparative Example 2, sticking occurred in 15 minutes, and production became impossible. In Comparative Example 3, sticking did not occur for 40 minutes during the filling test. In Comparative Example 4, sticking occurred in one minute, and production was not possible. In Comparative Example 5, sticking occurred in 5 minutes, and production became impossible.

A similar test was also conducted for a drug having a strong sticking property, such as ascorbic acid and acetaminophen. It has been found that capsules can be manufactured without sticking or the like of the granular material to which the material adheres or fills the capsule.
Next, Table 1 shows the results of the collapse test for Example 1 and Comparative Examples 1 to 3.

[0055]

[Table 1]

Each of the four capsules obtained in Example 1 and Comparative Examples 1, 2, and 3 was subjected to a disintegration test at N = 3 according to the Japanese Pharmacopoeia. The results are shown in the table. Example 1 exhibited the same level of disintegration as Comparative Example 1. On the other hand, in Comparative Examples 2 and 3, a delay in the disintegration time was observed. In particular, in the preparation of Comparative Example 3 which had an anti-sticking effect, the disintegration was significantly delayed. (Embodiment 2) In this example, an apparatus for producing a capsule agent for generating an air pulsation wave in a suction atmosphere will be described.

FIG. 7 is an overall configuration diagram schematically showing a capsule manufacturing apparatus according to the present invention. The capsule manufacturing apparatus 31 is the same as the capsule manufacturing apparatus 1 shown in FIG. 1 except for the following configuration. Therefore, the corresponding members are denoted by the corresponding reference numerals, and the description thereof is omitted. .

In the capsule manufacturing apparatus 31, an air pulsating wave generator 37 is connected between the lubricant collecting tank (hopper) 11 of the lubricant collecting pipe 10 and the air suction blower 13, An air supply device 8 is connected to the conduit 6. In this example, the air pulsation wave generator 37
As the air pulsating wave generator 7, one of a pair of connection ports is connected to an air suction device (blower for air suction) 13 and the other is connected to one end of a lubricant recovery pipe 10. ing.

When the air pulsating wave generator 37 is used, the air supply device 8 is driven to feed a constant amount and constant flow of air into the conduit 6, and at the same time, an air suction device (air suction blower) is used. 8) When the air pulsation wave generator 37 and the air pulsation wave generator 37 are driven, the air pulsation wave of the suction atmosphere, in which both the peak and the valley of the amplitude pulsate with the negative pressure, as shown in FIG. Occurs in chamber 5.

Also in this example, as long as the lubricant can be sufficiently diffused in the lubricant spraying chamber 5, the air pulsation wave generator 37
Alternatively, an opening / closing control valve may be used. When the on-off control valve is used, in the lubricant spraying chamber 5, a peak having an amplitude as shown in FIG. 8 (b) is at atmospheric pressure, and a valley is at negative pressure. Atmospheric air pulsation waves appear.

The air pulsation wave of the suction atmosphere is shown in FIG.
Any of the air pulsation waves shown in (b) can be used, but when the peaks of the amplitude are the atmospheric pressure and the valleys are the negative pressure, these are pneumatically transported when the air pulsation waves appear alternately. The lubricant alternates between moving and stopping in the conduit 6, and requires a large amount of energy to move the stopped lubricant again, whereas peaks and valleys of amplitude are generated. However, when air pulsation waves both having negative pressure are used, the lubricant which is pneumatically transported repeats slow movement and fast movement in the conduit 6, and is pneumatically transported in the conduit 6. Since the lubricant always moves, the energy for moving the lubricant can be reduced by the amount that the static friction coefficient does not matter, so rather,
The air pulsation wave of the suction atmosphere shown in FIG. 8A is more preferable.

In the first and second embodiments of the present invention, a press-type capsule filler having a funnel and a plunger has been described as an example of the capsule filler 2. The method for producing a capsule according to the present invention, the apparatus for producing a capsule according to the present invention, which is used for description, is not limited to a press-type capsule filling device, and may be an auger-type or disk-type. It is also applicable to a compressed type.

The amount of the lubricant to be sprayed on the contact portions S2a and S2b of the capsule filling device 2 which is in contact with the powder material is determined by the amount of the powder fluid to be in contact with the contact portions S2a and S2b which are in contact with the powder material. The trace amount required to prevent the adhesion of the material is sufficient, but is generally 0.0001% to 0.2% by weight of the capsule weight, preferably 0.001% to 0.1% by weight. % By weight.

The lubricant to be added to the granular material is
It may not be added, or may be about 0.001% by weight or more by weight.
You may mix in the range of less than weight%. Further, using a part of the amount of the lubricant used in the internal lubrication method, the air pulsating wave is used to apply the powder to the contact portion of the capsule filling device where the granular material contacts, and the content of the capsule is used. If the total amount of the lubricant of the product is adjusted to the weight of the lubricant used in the internal lubrication method, the powder material will be in contact with the powder material of the capsule filler compared to the conventional internal lubrication method Since it does not adhere to the contact surface,
It is possible to improve the production efficiency and produce a capsule which is not much different from the capsule produced by the internal lubrication method.

In the first and second embodiments of the present invention, an example is shown in which an air supply blower is used as the air supply means 8, but a gas cylinder or the like in which compressed gas is stored is used as the air supply means 8. Alternatively, a vacuum pump or the like may be used as the air suction means 13.

[0066]

In the method for producing a capsule according to the present invention and the apparatus for producing a capsule according to the present invention, the powder material of the capsule filling device is prepared under the condition that the lubricant is diffused by the air pulsating wave. Since the lubricant is applied to the contact portion in contact with the lubricant, the lubricant can be uniformly applied to the contact portion of the capsule filling device, in which the powder material is in contact, in a stable state. This allows the drug to be filled in the capsule (powder material)
However, even if it has a strong sticking property, the granular material taken out of the capsule filling device is encapsulated without the granular material adhering to the contact portion of the capsule filling device that comes into contact with the granular material. Can be filled inside. Further, since it is not necessary to use a lubricant in the content of the capsule to be produced, when the capsule is dissolved, the capsule can be produced in which the content of the capsule is also rapidly dissolved at the site.

Also, a predetermined amount of lubricant is added to a predetermined amount of the granular material, and a predetermined amount of the lubricant contained in the granular material is added to the granular material of the capsule filling machine. If the sum of the amount of the lubricant applied to the contact portion where the material contacts is adjusted to the weight of the lubricant used in the internal lubrication method, the production efficiency is improved, and the physical properties of the contents are improved. Capsules having substantially no difference in physical properties of the contents of capsules manufactured by the internal lubrication method can be manufactured.

[Brief description of the drawings]

FIG. 1 is an overall configuration diagram schematically showing a capsule manufacturing apparatus according to the present invention.

FIG. 2 is a schematic sectional view illustrating a configuration of an air pulsation wave generator.

FIGS. 3A and 3B are explanatory diagrams showing specific examples of air pulsation waves in a pressurized atmosphere.

FIG. 4 is a process chart showing a method for producing a capsule.

FIG. 5 is a process chart showing a method for producing a capsule.

FIG. 6 is a process chart schematically showing a method for producing a capsule according to the present invention.

FIG. 7 is an overall configuration diagram schematically showing a capsule manufacturing apparatus according to the present invention.

FIGS. 8A and 8B are explanatory diagrams showing specific examples of air pulsation waves in a suction atmosphere.

FIG. 9 is a process chart schematically showing a conventional method for producing a capsule.

FIG. 10 is a process chart schematically showing a method for producing a tablet described in Japanese Patent Publication No. 41-11273.

FIG. 11 is a process chart schematically showing a tablet production method described in JP-A-56-14098.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1, 31 Capsule manufacturing apparatus 2 Capsule filling device 2a Funnel 2b Plunger 3 Powder material storage tank 4 Dispensing table h4 Capsule fixing hole 5 Lubricant spray chamber 5a Open / close valve 5b Top cover 5h Doorway 6 Conduit 7,37 Air pulsation Wave generator 7a Case body 7b Rotary valve S7 Peripheral wall surface h7a, h7b Connection port 8 Air supply device 9 Lubricant storage tank 10 Lubricant recovery pipe 11 Lubricant recovery tank (hopper) 12 Air suction pipe 13 Air suction apparatus (Blower for air suction) 14, 16 Lubricant cut-out shutter 15 Lubricant supply pipe

 ──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Yasushi Watanabe 2874-752 Ohira, Numazu City, Shizuoka Prefecture (72) Inventor Sanji Tokuno 6-16-1 Flag Station, Shinagawa-ku, Tokyo

Claims (10)

[Claims] In a capsule manufacturing method, a capsule is filled with a predetermined amount of a granular material using a capsule filling device, and a lubricant is diffused by an air pulsating wave. Under the condition, a lubricant is applied to a contact portion of the capsule filling device where the powder material contacts, and a predetermined amount of the powder or granule is applied using the capsule filling device in which the lubricant is applied to the contact portion. A method for producing a capsule, wherein a material is taken out and a predetermined amount of the taken out particulate material is filled in a capsule. 2. The method according to claim 1, wherein the air pulsation wave is an air pulsation wave in a pressurized atmosphere. 3. The method for producing a capsule according to claim 1, wherein the air pulsation wave is an air pulsation wave in a suction atmosphere. 4. The amount of the lubricant applied to the contact portion of the capsule filling device where the granular material comes into contact is 0.0001% by weight or more and 0.2% by weight or less of the total weight of the capsule to be produced. The method for producing a capsule according to any one of claims 1 to 3, wherein 5. The method for producing a capsule according to claim 1, wherein a lubricant is not added to the predetermined amount of the granular material. 6. A predetermined amount of a lubricant is added to the predetermined amount of the granular material, and a predetermined amount of the lubricant contained in the granular material and the capsule filling device. The method according to any one of claims 1 to 4, wherein the sum of the amount of the lubricant applied to the contact portion where the particulate material of the present invention comes in contact with the lubricant is adjusted to the weight of the lubricant used in the internal lubrication method. A method for producing the capsule according to the above. 7. A powder material storage tank for storing a powder material filled in a capsule, a dispensing table for fixing a capsule body, and a predetermined amount of a capsule body fixed to the dispensing table. A capsule filling device provided for filling the granular material; a capsule filler provided for applying a lubricant to a contact portion of the capsule filling device where the granular material comes into contact; A lubricant spraying chamber for temporarily storing a contact portion with which the granular material contacts, an air pulsation wave generating means connected to the lubricant spraying chamber via a conduit, and an upstream side of the air pulsation wave generating means Air supply means provided in connection with, a lubricant storage tank connected to the conduit downstream of the air pulsation wave generation means, the air supply means and the air pulsation wave generation means Drive, into the conduit and lubricant spray chamber, Generating an air pulsation wave of a pressurized atmosphere, and diffusing the lubricant contained in the lubricant storage tank into the lubricant spraying chamber by the air pulsation wave of the pressurized atmosphere; A contact portion that comes into contact with the granular material of the present invention is accommodated in the lubricant spraying chamber, and a lubricant is applied to a surface of the contact portion that contacts the granular material of the capsule filling device; A predetermined amount of the granular material stored in the granular material storage tank is taken out using a capsule filling device in which a lubricant is applied to a surface of a contact portion that comes into contact with the powder, and a predetermined amount of the taken out powder is taken out. An apparatus for manufacturing a capsule, wherein a granular material is filled in a body of a capsule fixed to the dispensing table. 8. The air pulsating wave generating means includes: a cylindrical case body having a pair of connection ports on a peripheral wall surface; and dividing the case body around a center axis of the cylindrical case body as a rotation axis. And a rotary valve provided on the peripheral wall surface, one of a pair of connection ports provided on the peripheral wall is connected to the air supply means, and the other is connected to one end of the conduit. An apparatus for producing the capsule according to the above. 9. A predetermined amount of a particulate material storage tank for storing a particulate material to be filled in a capsule, a dispensing table for fixing a body of the capsule, and a body of the capsule fixed to the dispensing table. A capsule filling device provided for filling the granular material; a capsule filler provided for applying a lubricant to a contact portion of the capsule filling device where the granular material comes into contact; A lubricant spraying chamber for temporarily containing a contact portion with which the granular material comes into contact, a lubricant spraying unit for spraying a lubricant into the lubricant spraying chamber, and a lubricant spraying chamber connected to the lubricant spraying chamber. An air pulsating wave generating means provided; and an air suction means provided downstream of the air pulsating wave generating means and sucking air in the lubricant spraying chamber. The lubricant is sprayed into the lubricant spraying chamber, and the air absorption is performed. Driving the pulling means and the air pulsating wave generating means to generate an air pulsating wave in the lubricant spraying chamber, and the lubricant sprayed into the lubricant spraying chamber from the lubricant spraying means. The contact portion of the capsule filling device, which is in contact with the powder material, is accommodated in the lubricant spray chamber, and is spread on the surface of the contact portion that comes into contact with the powder material. Using a capsule filling device in which a lubricant is applied, and a lubricant is applied to the surface of a contact portion that comes into contact with the particulate material, the location of the particulate material stored in the powder material storage tank. An apparatus for producing a capsule, wherein a fixed amount is taken out and a predetermined amount of the taken out particulate material is filled in a body of a capsule fixed to the dispensing table. 10. The air pulsating wave generating means includes a cylindrical case body having a pair of connection ports on a peripheral wall surface, and the case body is divided with a center axis of the cylindrical case body as a rotation axis. And a rotary valve provided on the peripheral wall surface, one of a pair of connection ports provided on the peripheral wall surface is connected to the air suction means, and the other is connected to the lubricant spraying chamber. 9
An apparatus for producing a capsule according to claim 1.