WO2005000191A1

WO2005000191A1 - Method and apparatus for die-punching film-like oral drug

Info

Publication number: WO2005000191A1
Application number: PCT/JP2004/008658
Authority: WO
Inventors: Kazuya Yano; Tsutomu Awamura; Yasuo Hayashi
Original assignee: Kyukyu Pharmaceutical Co., Ltd.
Priority date: 2003-06-26
Filing date: 2004-06-14
Publication date: 2005-01-06
Also published as: JP4427981B2; JP2005013485A

Abstract

An apparatus for die-punching film-like oral drugs, comprising a cutting roll (11) having annular cutters (13) for punching out an oral drug layer (99) with a specified thickness formed on one surface of a resin film (98) in a specified drug shape, an anvil roll (12) used as an anvil for the cutting roll, and an adjusting mechanism adjusting a clearance between the cutting roll and the anvil roll so that the cutters of the cutting roll can punch out only the oral drug layer in the specified drug shape without reaching from an oral drug layer side to the rear surface of the resin film. Since the punched out drug layers (99a) are sucked and held continuously to the cutter side until the cutters are rotated and moved from a position where the cutters punch out the oral drug layers to a specified position (A) to peel off the punched out drug layers from the resin film. The drug layers sucked and held at the specified position (A) are carried to a next step by blowing out the drug layers. The residual oral drug layer (99b) after the punching out is moved and removed together with the resin film.

Description

Akira Itoda Punching molding method and punching molding apparatus for film-shaped oral agent for oral administration

The present invention relates to a film-shaped orally administered oral preparation formed by forming a edible intraorally administered substance among pharmaceuticals, quasi-drugs, cosmetics, foods and the like in a thin layer, and molding this into a predetermined dosage form. The present invention relates to a blanking method and a blanking apparatus for performing the blanking method.

Specifically, for example, transmucosal patches in the oral cavity such as the mucous membranes of the maxilla and gums, nasal mucosa, etc., patches for the prevention of oral diseases that are applied to affected areas in the oral cavity to treat and protect, and oral therapeutic patches Preparations, bad breath prevention patches, bad breath prevention patches, and oral medicines that dissolve in the oral cavity to be absorbed into the gastrointestinal tract and oral mucosa, as well as foods and deodorant and healthy maintenance effects TECHNICAL FIELD The present invention relates to a method and apparatus for punching a film-shaped oral administration agent which is formed into a thin layer and formed into a predetermined dosage form for oral administration products such as quasi-drugs and cosmetics having the above-mentioned actions. Background technology

Various techniques have been proposed in the past for making pharmaceuticals, quasi-drugs, cosmetics, foods, and the like into films or sheets for oral administration. In the present specification, the term “film” is used as a general term for thin layers such as a film and a sheet.

For example, Japanese Patent Application Laid-Open Publication No. 2001-50664 describes a sheet- or tape-shaped agent for oral administration of buprenorphine to the oral mucosa, and contains buprenorphine. It is described that a preparation solution for an intraoral administration layer is applied to a tape, sheet or oil, dried, and then separated as it is by cutting or perforating it into a dosage unit or a plurality of dosage units.

However, if the tape, sheet, or oil is cut or pierced with the orally administered drug layer as it is, the tape is cut from the cut material when administered into the oral cavity. It is troublesome to peel off the tape, sheet, or oil, and if you use a material such as tape, sheet, or file that does not feel uncomfortable in the oral cavity, the use of the material is naturally limited. However, the use of non-edible materials is more limited.

The following patent documents are provided to partially improve this.

Japanese Patent Application Laid-Open Publication No. 2001-504001 discloses that a preparation of an oral administration agent layer is prepared using a non-siliconized polyethylene terephthalate film, non-siliconized kraft paper, polyethylene-impregnated kraft paper, or non-silicon kraft paper. After coating on a suitable carrier material such as a polyethylene film and drying, the resulting film-shaped layer for oral administration is peeled off from the carrier material and cut into slices of a shape and size suitable for the intended use. To produce a film-form oral preparation.

Japanese Patent Application Laid-Open No. Hei 9-235220 describes a multi-layered film-form oral administration agent comprising a drug-containing layer, a non-adhesive layer and an adhesive layer. In addition, as a method for producing the composition, a preparation for oral administration layer is applied or sprayed onto a Teflon (registered trademark) petri dish, and the applied or sprayed preparation for oral administration layer is dried, and then a Teflon sealer is used. By repeatedly performing the peeling operation, a film-shaped oral administration agent having a required multilayer structure is obtained, and the prepared film-shaped oral administration agent is cut into a square, adhered to the same form of release paper, and then placed in an aluminum bag. A method of placing and packaging is disclosed in the examples. Japanese Patent Application Laid-Open No. 2001-288074, filed by the same applicant as the present application, discloses three types: a coating layer (a), a drug layer I (b), and a drug layer II (c). A film-like lozenge prepared by laminating the above layers in the order of a, b, c, b, a has been proposed. The method for producing an oral administration agent that is a film-like lozenge includes a method of forming a desired multilayer laminate structure by repeatedly spreading and drying each oral administration agent layer preparation on a polyester release film. A method of punching the obtained product into a circular shape having a diameter of 12 to 15 mm is described.

Japanese Patent No. 2555951 discloses that an oral administration agent layer preparation liquid containing a film forming agent, a gel forming agent, an active substance, an inert filler, and a polar solvent is coated on a silicone-coated paper by a coating device. After drying for 10 to 15 minutes at 80 ° C, as shown in Fig. 11, without drying the paper carrier 101, the dried material layer 102 A cutting line 103 defining a shape is formed therein by a suitable cutting machine, and a material layer 102 b remaining between the administration substance 102 a formed at the cutting line 103 is machined. Paper that is practically impermeable to water vapor, as a group of 12 dosing forms 102a, which are removed by mechanical stripping and left on a common paper carrier piece 101 as a group. It describes the production of a sheet-like oral dosage form by encapsulation in a composite packaging made of aluminum / ethylene vinyl acetate. When manufacturing a film-like orally administered agent having a multilayered structure described in the above-mentioned Japanese Patent Application Publication No. As shown in Fig. 2, an intermittently movable device for punching orally administered drugs is used. In this punch molding apparatus 110, a resin film 111 having a plurality of oral administration agent layers 112 formed on one surface is intermittently moved, and a resin film 111 is formed. The film is peeled off by the film peeling rolls 113 to form only the oral administration agent layer 112. Next, the orally administered drug layer 112 is punched out by a punching device 114 into a circular shape having a diameter of, for example, 15 mm. The punching device 1 14 is composed of a cutting blade 1 14 a that reciprocates up and down and a fixed plate 1 14 b with a through hole through which the cutting blade penetrates. When 1 2 stops at the position of the punching device 1 1 4, the cutting blade 1 14 a moves upward and penetrates the through hole of the fixing plate 1 1 4 b, and the oral administration agent layer 1 A circle with a diameter of 15 mm from 1 2 is punched. The punched circular oral administration layer is sucked by the suction pad 115 disposed above the fixing plate 114b, dropped on a conveyor (not shown), and sent to the packaging process. Can be After the circular oral administration agent layer is punched out, the remaining oral administration agent layer residue 112b is taken up by the waste take-up roll 116.

By using such a device for punching orally administered orally, a film-shaped orally administered orally having a required multi-layered structure can be obtained by using the above-mentioned JP-A-2001-5041106. It can be manufactured with better productivity than the conventional manual method described in JP-A-9-123520.

However, even if a device for punching orally administering an oral agent as shown in Fig. 12 is used, two sets of drive rolls 117a and holding holes 1 17b and waste winding holes 1 The orally administered drug layer 1 1 2 which is intermittently moved by 1 6 Variations in thickness are likely to occur, and depending on the material, it may be chipped and meander easily, requiring constant correction. In addition, the rotation speed of the driving roll is limited, and the processing speed cannot be increased. In addition, the residual oral administration agent layer residue 1 12 b after punching is considerably reduced in strength, and the drive roll 1 17 a and the holding roll 1 1 17 b and the waste take-up opening 1 It often breaks during the winding operation by 1 16 and there is a limit to increasing productivity.

In addition, as shown in FIG. 11, the orally administered agent obtained by the method of Japanese Patent No. 2555951 is placed on a common paper carrier piece 101 when administered orally. It is troublesome to occasionally peel off the 12 dosage forms 102a from the common paper carrier piece 101, and still has the same problem as the oral administration preparation of Patent Document 1. Moreover, the substance layer 102b remaining between the administration forms 102a is considerably reduced in the same way as the oral administration agent layer residue 112b in FIG. There is a possibility that it will be cut when it is peeled off and removed. Disclosure of the invention

Accordingly, an object of the present invention is to eliminate the inconvenience of peeling the orally administered drug from a paper carrier, a tape, a sheet, a foil, or the like when administering the orally administered film to the oral cavity. When formulating an intra-oral dosage form, the rotation speed of the drive roll can be increased without causing uneven thickness or meandering due to elongation during transfer of the intra-oral dosage form, and punching into a prescribed dosage form An object of the present invention is to provide a new and improved method and apparatus for punching and molding a film-like intraoral administration agent, which is not likely to be cut off when removing the remaining intraoral administration agent layer residue.

That is, the punching method of the film-form oral administration agent of the present invention,

A cutting blade for punching a prescribed thickness of the oral administration agent layer formed on one surface of the resin film into a prescribed dosage form is moved so as not to reach the oral administration agent layer side to the back surface of the resin film. An orally administered drug layer punching step of punching only the orally administered drug layer into a predetermined dosage form,

At the time of punching, the punched oral administration agent layer is sucked and held on the cutting blade side as it is And transferring the suctioned and held oral administration agent layer from the resin film by transferring the oral administration agent layer from the resin film; and

A step of blowing out the orally administered drug layer that is supplied to the next step by blowing out the punched orally administered drug layer that has been transported to a predetermined position in a state of being held by suction.

A preferred embodiment of the film-form oral administration agent of the present invention by the punching and molding method,

A resin film having an oral administration agent layer having a predetermined thickness formed on one surface is cut into a cutting roll having an annular cutting blade for punching the oral administration agent layer into a predetermined dosage form, and an anvil of the cutting roll. The gap is adjusted so that the cutting blade of the cutting roll does not reach the back surface of the resin film from the side of the oral administration agent layer while passing through the gap with the anvil roll. Oral administration agent layer punching out into a prescribed dosage form

A vent opening on the outer surface of the cutting roll body inside the annular shape of the cutting blade until the cutting blade rotates to a predetermined position with the rotation of the cutting roll after the cutting blade punches out the oral administration agent layer. From the above, the punched-out oral administration agent is maintained by suction-holding the punched-out oral administration agent layer inside the annular shape of the cutting blade through an air passage formed inside the cutting roll main body. An oral administration agent layer mouth peeling peeling step of peeling the layer from the resin film;

When the cutting blade is rotationally moved to the predetermined position, a gas is blown out from the ventilation port through the ventilation path, and the punched-out oral administration agent layer transported while being suction-held is blown out. Orally administered drug layer orifice to be supplied to the next step

—Le blowing process,

Is included.

Furthermore, the punching and molding apparatus for a film-like oral administration agent of the present invention,

A cutting blade for punching a prescribed thickness of the oral administration agent layer formed on one surface of the resin film into a prescribed dosage form is moved so as not to reach the oral administration agent layer side to the back surface of the resin film. An orally administered drug layer punching mechanism for punching only the orally administered drug layer into a predetermined dosage form, At the time of punching, the punched-out oral administration agent layer is sucked and held on the cutting blade side as it is, and is transported while being suction-held, thereby peeling the punched-out oral administration agent layer from the resin film. Supplying the next oral administration layer by blowing out the punched-out oral administration agent layer that has been transported to a predetermined position while holding it by suction.

It is characterized by having.

A preferred embodiment of the film-shaped oral administration agent according to the present invention by a punching and molding apparatus,

A cutting roll having an annular cutting blade for punching a predetermined thickness of the oral administration agent layer formed on one surface of the resin film into a predetermined dosage form, an anvil roll serving as an anvil of the cutting roll, and the cutting The gap between the cutting roll and the anvil roll is adjusted such that the cutting blade of the roll does not reach the back surface of the resin film from the oral administration agent layer side and punches only the oral administration agent layer into a predetermined dosage form. Adjustment mechanism, and

A vent is opened on the outer surface of the cutting roll body inside the annular shape of the cutting blade, and a ventilation path communicating with the vent is formed along the axial direction inside the cutting roll body, and the cutting blade is used for an intraoral administration agent layer. From the punching until the cutting blade rotates to a predetermined position in accordance with the rotation of the rotation of the cutting roll, sucks the ventilation path, and when the cutting blade rotates to the predetermined position, the ventilation path And a ventilation path suction / exhaust mechanism for blowing out the gas from the ventilation port through the air passage.

According to the above-described method and apparatus for punching out a film-like oral administration agent of the present invention, only the oral administration agent layer is punched out so that the cutting blade does not reach the back surface of the resin film, and the oral cavity is punched out as it is. By moving the dosage agent layer while holding it by suction, it is peeled off from the resin film and then blown out, so that an intraoral dosage agent without a resin film layer can be manufactured. As a result, a final product of an orally administered drug can be obtained without the trouble of peeling off the resin film when administered orally.

In addition, when the oral administration layer is transferred to the punching process or the punching mechanism, it is not transferred by the oral administration layer alone, but is transferred integrally with the resin film. The layer of the orally administered drug does not stretch during transfer, and as a result, thickness unevenness and meandering do not occur. In addition, the residual drug layer residue after punching the oral drug layer into a prescribed dosage form is also removed in a state integrated with the resin film. The layer residue can be reliably removed without breaking.

Furthermore, since the intraoral administration layer punched into the prescribed dosage form by the cutting blade is sucked, held, and transferred to the cutting blade as it is, the peeling from the resin film is effectively performed. When the intra-oral administration layer is sucked and held and transferred to a predetermined position, the intra-oral administration agent layer is blown out by blowing out the gas, so that it can be surely supplied to the next step.

In a further preferred embodiment of the film-shaped oral administration agent according to the present invention, the oral administration agent layer formed on one surface of the resin film comprises:

An oral administration agent layer forming step of applying and forming an oral administration agent layer of a predetermined thickness on the surface of the resin film,

The two intraoral administration agent layer-forming resin films having the same or different components formed in the intraoral administration agent layer formation step obtained in the above-mentioned intraoral administration agent layer forming step are placed such that each oral administration agent layer surface faces each other. An oral administration agent layer pressing step of bringing the oral administration agent layers into close contact with each other by applying pressure from the back surface of the resin film by superimposing;

A resin film separating step of peeling off only one of the two resin films laminated from the closely adhered intraoral administration agent layer;

To be formed.

The oral administration agent layer in the form of a laminated film thus formed on one surface of the resin film is formed by repeatedly applying and drying the preparation liquid for the preparation layer on the conventional resin film, and as many as desired. It can be manufactured with higher productivity as compared with the case of forming a lacquer, and the quantitative accuracy required for pharmaceutical preparations and the like can be remarkably improved as compared with the conventional method of layering.

In a further preferred embodiment of the method of the present invention for punching out a film-form oral administration agent, An oral administration agent layer formed on one surface of the resin film, an oral administration agent layer forming step of forming the oral administration agent layer of a predetermined thickness on the surface of the resin film,

A roll film forming step of forming a roll film by winding the orally administered agent layer-forming resin film obtained in the above-mentioned orally administered agent layer forming step into a roll shape;

While unwinding the two roll films each having the same or different component formed in the oral film layer obtained in the above-mentioned roll film forming step, each oral administration agent layer is superposed on each other so as to face each other. Pressing the roll film into the oral cavity by applying pressure from the back side of the film,

To be formed.

With this configuration, a laminated film-shaped oral administration agent can be manufactured in a batch system, the manufacturing apparatus becomes compact, and a desired number of formulation layers are laminated in a multilayer film. It is possible to manufacture the agent efficiently by using the pressure bonding method.

In a further preferred embodiment of the film-shaped oral administration agent punching and molding apparatus of the present invention, a moving mechanism for integrally moving the remaining agent layer punched out of the oral administration agent layer and the resin film. Is further provided.

With such a configuration, even if the residual agent layer has a reduced tensile strength, there is no possibility that the residual agent layer is cut, and the residual agent layer can be reliably and quickly moved and removed while being integrated with the resin film.

In a further preferred embodiment of the present invention, the cutting blade holding the punched-out oral administration agent layer by suction holds the punched-out oral administration agent layer to blow out gas from the vent. A suction pad arranged at a position facing the outer surface of the cutting blade roll body inside the annular shape of the cutting blade when the rotary blade is moved to the position, and sucking and holding the blown-out oral administration agent layer by a suction pad. Transfer to the next process. With such a configuration, the oral administration agent layer blown out from the cutting blade at the time of the closest approach between the cutting blade and the suction pad at a predetermined position surely jumps to the suction pad, is sucked and held by the suction pad, and proceeds to the next step. Can be efficiently transferred.

In a further preferred embodiment of the present invention, the cutting roll has a plurality of the annular cutting blades arranged in the circumferential direction and in the Z or axial direction. The ventilation holes opened in the outer surface of the roll body inside the annular shape of the cutting blades arranged in the circumferential direction correspond to the ventilation paths individually provided corresponding to the cutting blades arranged in the circumferential direction. Individually communicated separately. On the other hand, the ventilation holes opened on the outer surface of the roll body inside the annular shape of each cutting blade arranged in the axial direction communicate with the common ventilation path.

With such a configuration, it is possible to individually control the suction operation and the gas blowing operation through the air passage for each cutting blade, and the air passage suction / exhaust mechanism is effectively provided as the cutting roll rotates. Can be activated.

In a further preferred embodiment of the film-form oral administration device of the present invention, a plurality of vents arranged in a circumferential direction are opened on the outer surface of the anvil roll, and an air passage communicating with the vent is provided. Are formed along the axial direction inside the anvil roll, and a resin film suction mechanism is provided for sucking the air passage while the resin film is in contact with the outer surface of the anvil roll.

With such a configuration, the oral administration agent layer punched into a predetermined dosage form by the cutting blade of the cutting roll not only sucks and holds on the cutting blade side, but also anvils the resin film located on the back surface of the oral administration agent layer. Since it can be suction-held on the roll side, the punched-out oral administration agent layer can be more reliably peeled from the resin film.

The annular cutting blade includes not only a circular or elliptical shape but also a polygonal shape such as a rectangle, a square, a triangle, a hexagon, and an octagon, and the meaning of the term “annular” is understood in the broadest sense. And Brief Description of Drawings

Figure 1 shows a coating device for applying and forming an oral administration agent layer on a resin film It is explanatory drawing which shows an example of.

FIG. 2 is an explanatory view showing an example of a pressure bonding apparatus for forming a plurality of oral administration agent layers on a resin film.

FIG. 3 is an explanatory diagram showing an example of the operation of the crimping device of FIG.

FIG. 4 is an explanatory diagram showing an embodiment of the slipper device arranged in connection with the crimping device of FIG.

FIG. 5 is a perspective view showing an embodiment of the stamping and forming apparatus of the present invention.

FIG. 6 is an explanatory view showing another example of a pressure bonding apparatus for forming a plurality of oral administration agent layers on a resin film.

FIG. 7A is a perspective view showing an embodiment of a ventilation path intake / exhaust mechanism of a cutting roll used in the apparatus of FIG.

FIG. 7B is an exploded perspective view of FIG. 7A.

FIG. 8 is an exploded perspective view showing an embodiment of a film suction mechanism of an anvil roll used in the apparatus of FIG.

FIG. 9 is an explanatory view showing an embodiment of a gap adjusting mechanism for adjusting the gap between the cutting roll and the anvil roll used in the apparatus of FIG.

FIG. 10 is an explanatory view showing an embodiment of the suction pad used in the apparatus of FIG. FIG. 11 is an explanatory diagram showing a method for molding an orally administered drug according to a conventional technique. FIG. 12 is an explanatory view showing a conventional punching and molding apparatus for an orally administered drug. BEST MODE FOR CARRYING OUT THE INVENTION

In forming an oral administration agent layer (hereinafter abbreviated as “administration agent layer”) having a predetermined thickness on one surface of the resin film, a coating device 60 as shown in FIG. 1 can be preferably used. The coating device 60 guides the resin film 62 set on the resin film unwinding shaft 61 into the drying furnace 65 through the guide roll 63 and the doctor roll 64 to take up the resin film. The resin film 62 is continuously moved by being wound around the shaft 66. During this time, the administration layer preparation liquid 68 supplied to the administration layer preparation liquid supply dam 67 is applied onto the resin film. By adjusting the clearance between the resin film 62 above the doctor roll 64 and the doctor roll 64 to a predetermined dimension, a predetermined coating amount can be obtained (see a partially enlarged view). The coating layer 68 a on the resin film 62 thus formed is dried by hot air blown uniformly from the hot air blowing device 69 by passing through the drying furnace 65, and the administration agent layer is formed. The formed resin film 70 is wound around a winding shaft 66 in a roll shape.

Next, the resin film 70 for forming the dosage layer wound around the winding shaft 66 in the form of a roll is attached again to the winding shaft 61, and the dosage layer preparation liquid 68 of the same component or a different component is damped. The resin film is supplied to the part 67, and is again applied and dried, and is wound around the winding shaft 66, whereby a resin film having a two-layered administration agent layer formed thereon can be manufactured. By repeating the application and drying a plurality of times, it is possible to increase the thickness of the administration layer of the same component or to form a plurality of administration layers composed of various components.

However, the more the number of times of application and drying, the more inaccurate the application amount of the dosage layer preparation and the longer the time required for drying.Therefore, the number of times of application and drying is preferably about 2 to 3 times. Should be stopped only once. Further, the thickness of the administration agent layer formed on the surface of the resin film by one application is preferably about 1 to 300 m. If the thickness of one coating is greater than 30 O ^ m, the drying time will be too long and the productivity will be poor.

Using the coating apparatus 60 in FIG. 1, a single coating or a plurality of coatings of the same component or different components is applied, and a resin film 7 having a prescribed thickness of a dispensing agent layer formed on one surface 7 Produce 0. Each of the several types of resin film 70 formed in this manner was wound into a roll on a take-up shaft 66 to form a roll film. The two resin layer-forming resin films are pressed using the press-bonding device 80 thus formed, so that a film-shaped dosage agent layer having a multilayer structure in which many thin layers are laminated can be formed on the resin film.

That is, as shown in FIG. 2, one of the roll films 81 on which the dosage layer is formed is set on the upper unwinding shaft 83 of the crimping device 80, and the roll film on which the dosage layer is formed Set the other of 8 on the lower unwinding shaft 8 4. These mouths The film films 81 and 82 are unwound at predetermined speeds, respectively, and overlapped so that the surfaces of the administration agent layers face each other, and passed between a pair of pressure bonding rolls 85 and 85 to form a resin film. The pressure is applied from the back side, and the administration agent layers adhere to each other. When pressure is applied by the pressure rolls 85, 85, the temperature of the pressure roll is set to 30 to 150 ° C, preferably 30 to 100 ° C, and the product temperature of the administration agent layer is preferably set to 30 ° C. ~ 80 ° C. This temperature is slightly higher than the glass transition point of the thermoplastic edible substance in the dosage layer, and the temperature must be appropriately selected depending on the type of resin film, the type of substance used in the dosage layer, etc. There is. An excessively high temperature should be avoided because there is a danger that the dosage layer melts and the solvent in the dosage layer volatilizes and bumps occur. If the temperature is too low, sufficient adhesion may not be obtained. The pressure applied by the pressure roll is set to 0.05 to 0.5 MPa, preferably 0.1 to 0.7 MPa. Excessive pressure undesirably spreads the dosage layer and affects the quantitative accuracy per unit area. If the pressure is too low, sufficient adhesion cannot be obtained. The crimped product 86 that has passed through the crimping rolls 85, 85 has a structure in which both surfaces are covered with a resin film, and a plurality of administration agent layers are tightly laminated between them. When the crimped product 86 passes through the film peeling roll 87, the resin film 86 a covering the upper surface is peeled off, and the peeled-off resin film tip is wound up by a peeling film winding shaft 88. The resin film 86a can be continuously peeled off from the crimped product 86. The press-bonded product 86b thus obtained, that is, the resin film holding a plurality of administration layers on its surface, is wound into a mouth shape by a winding shaft 89, and a roll for holding a plurality of administration layers. A film 86c is formed. In the case where an administration layer is further laminated on the multiple administration agent layer holding film 86b, the following is performed. In other words, the multi-dose layer holding roll film 86c obtained above was removed from the winding shaft 89, and set on the upper unwinding shaft 83 in FIG. The roll film of the layer-holding roll film 86 c or the resin film 70 for forming the dosage-agent layer obtained by the coating device 60 of FIG. 1 is set on the lower unwinding shaft 84, and the above-mentioned crimping operation is performed. The same operation as above can be repeated.

Pass the two resin films holding the dosage layer between the pressure rolls 85, 85 W If air is entrapped between the two resin films during crimping, bonding failure will occur. In this case, without stopping the operation of the crimping device 80, as shown in FIG. 3, the gap between the pair of rolls 85a and 85a installed downstream of the crimping rolls 85 and 85 is reduced. While narrowing and closing, open the gap between the pressure rolls 85 and 85. By this operation, the air entrained between the two resin films is easily pushed out and removed by the closed rolls 85a, 85a. After the air has been removed, the crimping rolls 85, 85 can be closed and the rolls 85a, 85a can be opened to return to the normal crimping operation as shown in FIG.

When the crimping device 80 obtains a final crimped product holding a desired plurality of administration agent layers, the final crimped product is connected to a slit provided downstream of the crimping device 80. It is cut to a narrow width using one device 90. That is, as shown in FIG. 4, the crimped product 91 pressed by the press rolls 85, 85 has the resin film on the upper surface peeled off, and the final crimped product 9 la (the crimped product shown in FIGS. 2 and 3) 86 b may be the final crimped product). This final crimped product 9 la (e.g. dosage layer width 460 mm) is cut by slits 92 into 12 narrow crimped products 9 lb, e.g. 36 mm wide, and 12 reels Narrow width crimped products 9 1b are wound individually on 9 3a and 9 3b one by one. The slitter 92 has 13 blades 9 2b protruding in the circumferential direction and provided in parallel with each other on the outer circumference of one roll 9 2a, and is crimped as shown in FIGS. 2 and 3. When the product 86b is wound on the take-up shaft 89 as a crimping intermediate product, the slit between the slit 92 and the roll 94 below it is opened and the slitter 92 is opened. Does not work, and when the final crimped product 91a is cut into narrow widths, the gap between the slitter 92 and the roll 94 below it is closed, and the final crimped product 91a passing there Is cut into 12 narrow crimped products 9 1 b.

In the example shown in Fig. 4, the final crimped product 9 1a passes through slits 92 and is made into 12 narrow crimped products 9 1b, of which six odd crimped narrow crimped products Product 9 1b is wound on six reels 9 3a coaxially set on the product take-up shaft 9 5 arranged at the front.One each is wound on each of 9 reels, and even narrow rows of 6 narrow crimped products 9 lb 6 reels 9 3 b set coaxially on the product take-up shaft 89 arranged behind W Each one is wound up. The scraps 9 1 c cut at both ends of the final pressure-bonded product 91 a cut at the slit 92 are wound up by a scrap winding shaft 96.

The narrow width compression-bonded product 91b (width 36mm) cut in this manner is converted into a film-form oral administration agent of a predetermined dosage form by using the punching molding method and the punching molding device of the present invention. Can be molded.

FIG. 5 shows an embodiment of the stamping and forming apparatus of the present invention. The narrow width crimped product 91b wound in a roll shape on the reels 93a and 93b in FIG. 4, that is, one resin film is formed. The pressure-bonded product in which the dispensing agent layer 99 having a predetermined thickness is held on the surface of the resin film 98 that has been peeled off is continuously unwound and sent to the punching and molding apparatus 10. The punch forming apparatus 10 is composed of a cutting roll 11 having a circular annular cutting blade 13 having a diameter of, for example, 15 mm protruding from the outer peripheral surface of the rotating roll, and an anvil roll 12. When the press-bonded product is continuously introduced between 1 and 2, and when the press-bonded product is sandwiched between the nozzles 11 and 12, the cutting blade 13 protruding from the cutting roll 1 1 1 Only the dosage form layer 99 is punched out so as not to reach the back of the film 98. The cutting depth by the cutting blade 13 can be controlled by adjusting the gap between the cutting roll 11 and the anvil roll 12 by a gap adjusting mechanism (see FIG. 9) described later.

In FIG. 5, the cutting roll 11 and the anvil roll 12 are shown apart from each other for easy understanding, but the actual cutting operation is performed by disposing the cutting roll 11 at a position indicated by a one-dot chain line. It is done.

Further, in the example shown in the figure, there are two rows in which a plurality of cutting blades 13 are arranged at equal intervals in the circumferential direction of the cutting roll 11, and two cutting blades 13 are provided in the axial direction of the cutting roll 11. It is parallel. However, the number of rows arranged in the circumferential direction and the number arranged in the axial direction can be set to an appropriate number according to the dimensions of the dosage agent, the width of the dosage layer, and the like.

When punching only the dispensing agent layer 9 9 with the annular cutting blade 13, the cutting roll 11 1 has an air passage formed along the axial direction inside the main body (Fig. 5 shows only the end opening 21 a of the air passage. The dosing agent layer 99a punched out in a circular shape by suctioning from the air passage intake / exhaust mechanism (see Fig. 7) described later 11 is sucked and held on the outer surface of the main body, and is transported in the direction of the arrow X with the rotation of the cutting roll 11 in this state.As a result, the punched administration layer 9 9 a is peeled off from the resin film 98. Is done. In the suction by the air intake / exhaust mechanism, suction may be started before the punching operation is started, suction may be started in the middle of the punching operation, or suction may be started immediately after the punching operation is completed. You may.

The annular cutting blade 13 may have a polygonal shape such as a rectangular shape, a rectangular shape, a triangular shape, a hexagonal shape, an octagonal shape, as well as a circular or elliptical shape.

The cutting blade 13 and the punched dosing layer 99 a sucked and held in the cutting blade 13 are rotationally moved to a predetermined position (for example, the position A in FIG. 5) with the rotation of the cutting roll 11. At this point, the administration layer 9 9a, which was sucked and held inside the annular cutting blade 13 by being blown out by the air intake / exhaust mechanism, is discharged and transferred from the cutting roll 11 to the next process. (Not shown in FIG. 5). After the dosing agent layer 9 9a punched out in a circular shape is peeled off and removed, the remaining agent layer residue 9 9 b remains in the resin film 98 and remains in the drive roll 14 and the holding roll. After passing through a pair of rolls including the rolls 15, the rolls are wound as a scrap take-up roll 16. At this time, the residual agent layer waste 9b can be moved by a set of rolls composed of the driving roll 14 and the holding roll 15 or a moving mechanism composed of the waste take-up opening 16.

In the above description, an example of a batch operation in which a resin film having a single or multiple dosage agent layers formed on one surface is once wound into a roll and punched and formed into a roll film. The invention has been described. However, the continuous operation in which the dosage layer-formed resin film obtained by the coating device 60 or the press-fitting device 80 is directly transferred to the punching and forming device 10 without being formed into a roll film and punched and formed. However, it is possible to implement the present invention.

Further, in the above description, the administration agent layer-forming resin film 70 obtained by the coating apparatus 60 in FIG. 1 was once wound into a roll by a winding shaft 66 to form a roll film. The other pressure-sensitive adhesive layer 80 is pressed against another resin layer-forming resin film. However, as shown in FIG. 6, before the resin layer forming resin film 70 sent out from the drying furnace 65 of the coating device 60 is wound into a roll, It is also possible to directly press-bond the synthetic resin film and another dosage agent layer-forming resin film 71 near the outlet of the drying furnace 65. That is, two dispensing agent layer forming resin films 70 and 71 are superimposed on each other so that their dispensing agent layer surfaces face each other, and a set of crimping rolls 7 installed near the drying furnace 65 outlet of the coating apparatus. By pressing through the back surface of the resin film through 2, 72, a directly press-bonded product can be obtained. This pressed product is passed through a film peeling roll 73 to peel off the resin film on the upper surface, and the peeled resin film is wound up by a peeling film winding shaft 74 to continuously peel off the resin film. The multi-administration agent layer-forming roll film 75 can be obtained by winding the film into a roll shape by using 66.

FIG. 7 is an explanatory view of an embodiment of a ventilation path intake / exhaust mechanism of the cutting roll 11. As shown in FIG. 7A, an administration layer is formed on the outer surface of the main body of the cutting roll 11 in a predetermined dosage form. A plurality of annular cutting blades 13 are arranged so as to be arranged in two rows in the circumferential direction of the cutting roll, and are provided so as to project in parallel with each other in the axial direction of the cutting roll. An annular inner side cutting roll 11 is provided on the outer surface of the main body with a vent 20 having a set of a plurality of (four in the illustrated example) small holes. Rotating shafts 11a and lib protrude from both ends of the cutting roll 11 in the axial direction. These rotating shafts are rotatably supported by bearing blocks 17a and 17b, and are driven by a driving device (not shown). It is driven to rotate.

As can be seen from Fig. 7B with the cutting hole 11 removed from the bearing blocks 17a and 17b, the cutting roll 1 1 has a plurality of air passages 21 along the axial direction inside the main body. (For simplicity, only one ventilation passage 21 is shown by a dotted line in the figure), and both ends of these ventilation passages 21 are connected to the axis of the cutting roll body. Direction An opening is formed on the end face, and an end opening 21a is formed. In addition, ventilation holes 20 opened inside the annular shape of each cutting blade 13 arranged in the circumferential direction of the cutting roll 11 are provided with ventilation passages 21 provided individually for each cutting blade. Are individually and individually communicated. Also, as shown in the figure, when a plurality of (two in the illustrated example) annular cutting blades 13 are arranged in parallel in the axial direction of the cutting roll 11, they are arranged in parallel in the axial direction. A ventilation port 20 opened inside the annular shape of each cutting blade 1 3 communicates with one common ventilation path 21. Further, as shown in FIG. 7B, when the rotating shafts 11a and 11b of the cutting roll 11 are supported by the bearing blocks 17a and 17b, the axial end face of the cutting roll On the surfaces of the bearing blocks 17a and 17b that abut, there are formed through holes 18a and 18b of the rotating shaft, and one bearing block 17a has a cutting roll end face. A circumferential recess 22 having a length equivalent to approximately 1/4 of the circumference and a circular recess 23 are formed, and the circumferential recess 22 communicates with a suction port 22 a opening on the side of the bearing block. The circular recess 23 communicates with a gas inlet 23 a opening on the side of the bearing block. The surface of the other bearing block 17b has only a through hole 18b for the rotating shaft, and the surface blocks and seals the other end opening 21a of the ventilation path 21. ing.

The operation of the above-described ventilation path intake / exhaust mechanism including the ventilation port 20, the ventilation path 21, the circumferential recess 22, the suction port 22 a, the circular recess 23, and the gas blowing port 23 a is as follows. It is.

When the dispensing agent layer forming resin film is transported and caught in the gap between the cutting roll 11 and the anvil roll 12 of the punching molding apparatus 10 in FIG. 5, it is rotated in the direction of the arrow X in FIG. 7A. The annular cutting blade 13 rotating to the lowermost part of the outer peripheral surface of the cutting roll 11 punches out only the administration agent layer so as not to reach the back surface of the resin film. At this time, the ventilation path 21 communicating with the ventilation hole 20 inside the annular cutting blade 13 performing the punching operation should communicate with the lowermost part of the circumferential recess 22 of the bearing block 17a. As a result, the dosing agent layer which is in communication with the suction port 22 a that continues to be sucked, is suctioned from the ventilation port 20 through the circumferential recess 22 and the ventilation path 21, and is punched out, is closed by the ring of the annular cutting blade. The suction roll is held by suction on the outer surface of the cutting roll body inside the shape (see Fig. 5, 99a). The suctioned holding state of the punched administration layer is maintained while the ventilation path 21 moves with the rotation of the cutting roll 11 and the end opening 21 a communicates with the circumferential recess 22. Therefore, it is possible to control the maintenance time of the suction holding state by adjusting the length of the circumferential recess 22.

Along with the rotation of the cutting roll 11, the air passage 21 communicating with the cutting blade 13 that holds the punched dosing agent layer by suction is rotated, and the end opening 21a is positioned at a predetermined position, that is, as shown in FIG. 7 Move to the position of the circular recess 23 in B (corresponding to the position A in Fig. 5). When the gas comes in, the gas is communicated with the gas blowing port 23 a maintained in a predetermined pressurized state, so that the gas is discharged from the ventilation port 20 through the circular recess 23 and the ventilation path 21. The administration agent layer which has been blown out and sucked and held inside the annular cutting blade 13 is blown out and supplied to a transfer means for a next step, for example, a packaging step.

Cutting Roll 1 1 Ventilation path 2 1 formed inside the main body, circumferential recess 22 and circular recess 23 are securely connected, and the end faces of bearing blocks 17 a, 17 b and cutting roll 11 are connected. It is preferable that the bearing blocks 17a and 17b be pressed against the cutting roll 11 main body end face by the springs 19 and 19 so as to hermetically seal the bearing rolls 17a and 17b. In the embodiment shown in FIG. 7, both ends of the air passage 21 are opened as end openings 21a on both end surfaces of the cutting roll body, and the circumferential recess 22 and the circular recess 23 are formed on one bearing block. However, in this case, the end opening 21a of the ventilation path is closed at the end face of the cutting roll body that is in contact with the other bearing block 17b without opening. Is also good. Needless to say, the circumferential recess 22 and the suction port 22 a and the circular recess 23 and the gas blowing port 23 a constituting the ventilation path intake / exhaust mechanism are provided in both the bearing blocks 17 a and 17 b. Is also good.

Further, in the embodiment shown in FIG. 7, the circular passage 23 and the air passage 21 are formed by communicating the air passage 21 with the gas blowing port 23 a in which the gas is maintained in a predetermined pressurized state. The gas was blown out of the vent hole 20 through the valve. However, when the gas passage 21 communicated with the circular recess 23, a valve was installed upstream of the gas inlet 23a (Fig. (Not shown) may be opened and closed so that gas is blown out from the gas blowing port 23a for a short time. By blowing the gas by opening and closing the valve in this manner, the timing of delivery to the suction pad 50 described later can be adjusted more finely. In addition, as the gas from the gas blowing port 23a, in addition to aseptic air, an inert gas such as aseptic nitrogen gas may be mentioned.

As described with reference to FIG. 5, the punched administration layer 99a is moved with the rotation of the cutting roll 11 while being sucked and held inside the annular cutting blade 13 by the rotation. The withdrawn dosage form layer 9 9 a is peeled off from the resin film 98, but in order to surely peel off from the resin film, the resin film 98 in contact with the anvil roll 1 (2) It is better to keep the suction on the outer surface. Good. FIG. 8 shows an embodiment of a resin film suction mechanism for sucking and holding the resin film 98 on the outer surface of the anvil roll 12, which is the same as the ventilation path suction and exhaust mechanism of the cutting roll 11 shown in FIG. In addition, a plurality of air holes 30 each having a plurality of (four in the illustrated example) small holes are formed on the outer surface of the anvil roll 12 on which the resin film 98 is in contact with the eight surfaces, and the cutting roll 11 shown in FIG. Are arranged and opened at the positions corresponding to the vents 20 in the above, and are individually connected to the ventilation paths 31 provided individually corresponding to the respective vents 30 (in the figure, the simplification is made). Only one ventilation channel 31 is shown with a dotted line). Further, when the rotating shaft 12a of the anvil roll 12 is supported by one of the bearing blocks 35a, the surface of the bearing block 35a with which the axial end face of the anvil roll comes into contact is provided with the rotating shaft 1a. In addition to the through hole 3 6a of 2a, a circumferential concave portion 32 having a length corresponding to approximately 1Z2 circumference of the anvil roll is formed, and the circumferential concave portion 3 2 is a bearing block 35a. It communicates with the suction port 32a opened on the side. In the other bearing block 35b, only the through-hole 36b that supports the rotating shaft 12b of the anvil roll 12 is formed on the surface in contact with the axial end face of the anvil roll 12. The other end opening 31a of the air passage 31 is closed and sealed.

The operation of the above-described resin film suction mechanism composed of the above-described ventilation port 30, ventilation path 31, circumferential recess 32, and suction port 32 a is as follows.

When the resin layer forming resin film is transported and caught in the gap between the cutting roll 11 and the anvil roll 12 of the punching molding apparatus 10 in FIG. The anvil roll 12 is moved while rotating while contacting the right half circumference, but communicates with the air vent 30 opened at the lower surface of the resin film while the resin film 98 is in contact with the outer surface of the anvil roll. The ventilation path 3 1 and the end opening 3 la communicate with the circumferential recess 3 2 of the bearing block, thereby communicating with the suction port 3 2 a maintained in a reduced pressure state, and the circumferential recess 3 2 and the ventilation path. The resin film 98 is sucked through the vent hole 30 through the hole 1 1, and the resin film 98 can be sucked and held on the outer surface of the anvil roll 1 2. Ensure separation from ILM 98 It can be.

The circumferential concave portion 32 and the suction port 32 a constituting the resin film suction mechanism of the anvil roll 12 are also provided with the ventilation passage suction and exhaust device of the cutting roll 11. Similarly to the structure, it may be provided on both bearing blocks 35a and 35b, or may be provided on only one bearing block 35a.

FIG. 9 is an explanatory view of an embodiment of the gap adjusting mechanism 40 for adjusting the gap between the cutting roll 11 and the anvil roll 12 shown in FIG. 5, and includes a cutting roll bearing block 17a and an anvil roll. The bearing block 35a is urged by an air cylinder (not shown) from the outside (upward in the figure) so as to be close to each other, and the bearing block 17a of the cutting roll is Insert a wedge 41 between the anvil roll bearing block 35a and place the flat bottom surface of the wedge 41 on the flat surface of the top surface of the anvil roll bearing block 35a. The tapered surface of the bottom surface of the cut roll bearing block 17a is placed on the tapered surface of the top of. A screw 4 2 is screwed into the wedge 4 1, and the handle 4 4 is attached to the base end of the screw 42 by penetrating the flange 43 of the anvil roll bearing block 35 a. The screw 42 can be rotated by the handle 44, and the wedge 41 can be moved in the arrow Y direction by rotating the screw. By rotating the screw 4 2 and moving the wedge 4 1 toward the tip of the screw 4 2 (to the right in the drawing), the gap between the cutting roll and the anvil opening can be expanded. The gap can be narrowed by moving it toward the base end (to the left in the drawing). By such a gap adjusting mechanism 40, the cutting blade 13 of the cutting roll 11 cuts through only the dispensing agent layer 99 without reaching the back surface of the resin film 98 so that the cutting is performed by the cutting blade. The depth can be controlled with high accuracy.

FIG. 10 shows the case where the punched administration layer 99 a is rotated and moved to a predetermined position (A position) while the punched administration layer 99 a is suction-held inside the annular cutting blade 13 as shown in FIG. Next, an embodiment of the suction pad 50 for transferring the administration agent layer blown out by blowing out the gas from the vent to the next step is shown. That is, a suction pad rotating shaft 51 is arranged near the cutting roll 11 in parallel with the axis of the cutting roll, and the rotating shaft 51 is attached to four suction pads to be extended by 90 ° in the radial direction. A pair of suction pads 50-1, 50-2, 50-3, 50-4 are provided at the tip of each arm, respectively. Each time the arm 52 moves 90 ° due to the rotation, each suction pad 50 sequentially faces the cutting roll 11 inside the annular cutting blade 13 of the annular cutting blade 13. It has been taken.

Inside each arm 52, a ventilation path 53 (shown by a dotted line) communicating with the suction pad 50 is formed, and a plurality of these ventilation paths 53 are formed inside the rotation shaft 51 in the axial direction (the example in the figure). Each of which has four) air passages (not shown) '. Each of these ventilation paths has a port communicating with a pressure reducing source similar to the circumferential recess 22 in the bearing block 17 a of the cutting roll 11, and a port communicating with a pressurized gas source similar to the circular recess 23. Each of the suction pads 50 and 50 is switchably connected to each other, so that suction and blowing of gas can be individually performed on each suction pad 50 through the air passage 53.

Below the suction pad rotating shaft 51, a transport conveyor 54 as a transfer means in the next packaging process is arranged.

The operation of the suction pad 50 having such a configuration will be described below.

As described above, the punched dosing layer that has been sucked and held inside the annular cutting blade 13 and rotated with the rotation of the cutting roll 11 is positioned at a predetermined position A in the circumferential direction of the cutting roll (see FIG. 5). ), The gas is blown out from the cutting blade 13 by blowing out the gas from the vent opening inside the annular cutting blade. At this time, the dosage layer blown out from the cutting blade 13 jumps to the first suction pad 50-1, which is in the suction state and has been rotated to the position a facing the cutting blade 13. Adsorbed and held. Even if there is a gap of about several mm at the closest position between the cutting blade 13 and the suction pad 50-1, the administration layer is blown out from the cutting blade 13 and suction operation is performed by the suction pad 50-1. As a result, the dosage layer surely jumps to the suction pad 50-1 and is held by suction.

The first suction pad 50 -1 is further rotated 90 ° while holding the dosage layer adsorbed and reaches a position “b”, and is brought into a gas-blowing state, and the dosage layer adsorbed and held 9 9 a is dropped onto the conveyor 54. The punched administration agent layer 99a is transferred by the transport conveyor 54 in the packaging process which is the next process.

When the first suction pad 50-1 reaches the position "b", the second suction pad 50-0-2 which is provided at a 90 ° offset from the first suction pad 50-1 and is in a suction state is set. Is located at a position facing the next annular cutting blade 13 which has been rotated to the predetermined position A in the circumferential direction of the cutting roll. The dosing agent layer blown out from the cutting blade 13 by suction. In this way, the first to fourth suction pads 50-1, 50-2, 50-3, 50-4 are sequentially moved from position a to position d with rotation of the rotating shaft 51. During this time, suction is performed from position a to just before position b, and gas is blown out at position b.Adsorption pad 50 repeatedly holds suction agent layer 99a and holds it down to the conveyor. Is Also, each time the suction pad 50 rotates 90 °, the suction is performed such that the cutting blades 13 arranged in multiple stages at equal intervals in the circumferential direction of the cutting roll 11 move in the circumferential direction one by one. The rotation of the pad 50 and the rotation of the cutting roll 11 are synchronized.

Although four suction pad mounting arms 52 are provided at 90 ° intervals in the embodiment shown in FIG. 10, the rotation of the suction pad 50 and the rotation of the cutting roll 11 are synchronized. If it is possible, an appropriate number of arms 52 for attaching suction pads can be provided at equal intervals. Further, as shown in FIG. 7A, a plurality of annular cutting blades 13 are arranged in multiple stages at equal intervals in the circumferential direction on the outer periphery of the cutting roll 11, and two in each stage are provided in parallel. Therefore, a pair (two) of suction pads 50 are also provided at the tip of each arm 52. Each of the suction pads 50 is provided in accordance with the number of cutting blades 13 provided on the cutting roll 11. The same number of suction pads 50 as the number of cutting blades 13 can be provided at the tip of each arm 52. Alternatively, according to the number of arms 52 provided with one suction pad 50 at the tip thereof and the number of cutting blades 13 provided on the cutting roll 11, the suction pad rotating shaft 50 may be provided. May be provided.

Although this adsorption pad is an effective means for reliably transferring the punched administration layer 99a to the next step, it can be omitted. For example, a punching and forming apparatus in which the vertical relationship in FIG. 5 is completely reversed is obtained, and the cutting roll 11 is rotated to be punched into the annular cutting blade 13 and the administration layer 99 a sucked and held at the lowest position. At this time, the dosage layer 99a may be blown out from the cutting blade 13 and dropped directly onto the transport conveyor 54, for example.

The dispensing agent layers of the two resin films on which the dispensing agent layers are formed are overlapped so as to face each other, and after being crimped by the crimping device 80 shown in FIG. When manufacturing a resin film in which a plurality of administration layers are laminated, at least the administration layer is formed on the resin film to be peeled off. It is desirable to apply a hydrophobic substance to the surface (surface) to perform a release treatment in advance, so that the resin film can be easily removed from the administration agent layer. When a resin film holding a single or a plurality of administration layers is wound into a roll to form an oral film, the surface of the resin film on which the administration layer is not formed when rolled is used. (The back side) also comes into contact with the administration agent layer. At this time, if the back surface of the resin film is not easily peeled off from the administration agent layer, it becomes difficult to rewind the roll film. Therefore, when the resin film holding the dosage layer is used as a roll film, the resin film to be peeled is subjected to a peeling treatment in advance on both the surface on which the dosage layer is formed and the back surface opposite thereto. On the other hand, it is preferable that the resin film holding the administration layer without being peeled is subjected to a release treatment in advance on at least the back surface on which the administration layer is not formed.

As the hydrophobic substance to be coated on the resin film during the peeling treatment, silicone resin or wax (honey bee) conforming to the standard for food additives can be used. In addition, metal foil such as aluminum foil or tin towel is used. You can also do it. Examples of the resin film serving as a base film for holding the dosage form layer include polyethylene terephthalate, polyethylene naphthalate, copolymerized polyester, polyimide, polypropylene, cellulose triacetate, vinyl acetate resin, and ethylene-vinyl acetate copolymer. It can be appropriately selected from films made of resins such as polyethylene, polyvinyl chloride, polycarbonate, polypropylene, triacetate, and fluororesins (ETFE, PFA, FEP). In particular, polyethylene terephthalate (PET) can be preferably used.

The administration agent layer formed on the surface of the resin film may be formed as a single layer, but usually, an appropriate number of various layers suitable for exhibiting a desired medicinal effect or function are laminated. It is formed as a laminated structure composed of a plurality of layers. The general laminated structure of a film-shaped oral administration layer is composed of a coating layer that constitutes the outermost layer, a drug layer that contains the base of the formulation and the active ingredient, and, if necessary, a support layer, etc. It has been done. In this specification, the term “administration agent layer” is used as a general term for a coating layer, a drug layer, a support layer, and the like.

The coating layer has the function of protecting the surface of the film It has the function of improving the dring or the function of adhering to the oral mucosa when used as a patch. For example, the following substances can be used alone or in appropriate combination.

Polyvinyl pyrrolidone, gelatin, polyvinyl alcohol, sodium polyacrylate, starch, xanthan gum, karaya gum, hydroxypropyl cellulose, water-insoluble methacrylic acid copolymer, ethyl methacrylate / methacrylic acid trimethylammonium methyl Polymers, dimethylaminoethyl methacrylate / methyl methacrylate copolymer, carboxybier polymer, polyacrylic acid, partially cross-linked polyacrylic acid, Ripichi popol, tragacanth, arabic gum, locust beans gum, guar gum, Dextrin, dextran, amylose, hydrated xylated alkylcellulose ether, polyacrylic acid, alkali metal polyacrylates, polyacrylates, rosin-based resins (gum rosin, wood Mouth gin, tall oil rosin, disproportionated rosin, hydrogenated rosin, maleated rosin, etc.), delacant gum, pullulan, chitosan, water-soluble pullulan ether, water-soluble pullulan ester, casein, alkyl alginate, alkyl polyacrylate Stell, polyacrylate etc.

As the base used together with the active ingredient in the drug layer, for example, the following substances can be used alone or in appropriate combination.

Polyvierpyrrolidone, polyvinyl alcohol, sodium polyacrylate, carboxymethylcellulose, starch, xanthan gum, karaya gum, sodium alginate, methylcellulose, dextrin oxyvinyl polymer, agar, hydroxypropylcellulose, hydroxypropyl methylcellulose Evening rate

(HPMCP), Cellulose acetate phthalate (CAP), Carboxymethylethylcellulose (CMEC), Acrylic acid polymer (Acrylic esters such as butyl acrylate, 2-ethylhexyl acrylate, etc.) , Methacrylic acid polymers (eg, methyl acrylates such as methyl methacrylate), maleic anhydride polymers (eg, copolymers such as methyl vinyl ether), ethyl cellulose, hydroxyethyl cellulose, and hydroxypropyl methyl cellulose. , Methacrylic acid, carbopol, tragacanth, gum arabic, oral bean gum, guar gum, power lage Nan, dextrin, dextran, amylose, hydroxylated alkylcellulose ether, alkali metal carboxymethylcellulose, alkali metal polyacrylates, polyacrylates, rosin-based resins (gum rosin, wood rosin, 1-oil rosin) , Disproportionated rosin, hydrogenated rosin, maleated rosin, etc.), delacant gum, pullulan, chitosan, water-soluble pullulan ether (pullulane methyl ether, pullulan ethyl ether, pullulan pill ether, etc.), water-soluble pullulan ester (pullulan acetate) , Pullulan ethylate), cellulose dibasic acid monoesters, starch and saccharide polyhydric alcohol dibasic acid monoesters, polyvinyl alcohol and polyvinyl alcohol derived Dibasic acid monoesters, copolymers of maleic anhydride with vinyl acetate or vinyl monomers such as styrene and vinyl methyl ether, copolymers of acrylic acid and methacrylic acid with other vinyl monomers, Ethyl methylcellulose, carboxymethylhydroxyethylcellulose, carboxylethylcellulose, carboxymethylethylcellulose, carboxymethylstarch, plango goose coat, galactomannan, propylcellulose, Eudragit, cellulose acetate phthalate, hydroxy Propyl cellulose phthalate, polyvinyl alcohol phthalate, styrene maleic anhydride copolymer, casein, alkyl alginate, alkyl polyacrylate, and the like.

The support layer is for preventing the active ingredient from being eluted into the non-target portion in the oral cavity.For example, the following substances are used alone or in an appropriate combination to form a layer that is hardly soluble or insoluble in the oral cavity. By doing so, the purpose can be achieved. Gelatin, carboxymethylcellulose, methylcellulose, propyloxyvinyl polymer, agar, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), carboxymethylethylcellulose (CMEC), acrylic acid heavy Acrylates such as butyl acrylate and 2-ethylhexyl acrylate, etc., methacrylic acid polymers (such as methacrylic acid esters such as methyl methacrylate), and maleic anhydride polymers (such as methyl vinyl ether). Copolymer, etc.), ethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcell mouth Ethyl cellulose, cellulose acetate phthalate with a degree of substitution of ethoxy group of 1.5 or more, cellulose acetate phthalate, mouth-to-mouth bean gum, guar gum, power ragenan, hydroxylated alkyl cellulose ether, alkali metal Carboxymethyl cellulose, rosin resin (gum rosin, wood rosin, tall oil rosin, disproportionated rosin, hydrogenated rosin, maleated rosin, etc.), shellac resin (shellac, white transparent shellac), cellulose dibasic acids mono Esters (cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate phthalate, methylcellulose phthalate, ethyl octlodoxetyl cell mouth sulfurate, cellulose acetate meleate, etc.), starch and Dibasic acid monoesters of polyhydric alcohols (starch acetate, amylose acetate, dextrin, lactose, saccharose, darcos, galactose, fructose, sorbose, rhamnose, xylose, Phthalic acid monoesters such as mannitol, sorby] ^-vinyl), polyvinyl alcohol and dibasic acid monoesters of polyvinyl alcohol derivatives (polyvinyl acetate phthalate, polyvinyl phthalate, polyvinyl butyrate) —Tophthalate, polyvinylacetate phthalate, polyvinylacetate succinate), copolymers of maleic anhydride with vinyl monomers such as vinyl acetate or styrene and vinyl methyl ether (styrene · Water Maleic acid copolymer, Vinyl methyl ether Maleic anhydride copolymer, Ethylene Maleic anhydride copolymer, Vinyl butyl ether Maleic anhydride copolymer, Acrylonitrile Methyl acrylate Maleic anhydride copolymer Copolymer, butyl acrylate / styrene / maleic anhydride copolymer), copolymer of acrylic acid and methacrylic acid with other vinyl monomers (styrene / acrylic acid copolymer, methyl acrylate / acrylic acid copolymer) Union, methyl acrylate / methyl acrylate copolymer, methyl methacrylate / methacrylic acid copolymer, butyl acrylate / styrene / acrylic acid copolymer), ethyl methyl cellulose, carboxymethyl hydroxyethyl cellulose, carboxy Shetylcellulose, calpo Xymethylethyl cellulose, carboxymethyl starch, plantago seed coat, galactomannan, propylcellulose, Eudragit, cellulose acetate Tophylate, hydroxypropyl cell mouth phthalate, polyvinyl alcohol phthalate, etc.

Examples of drugs that can be used as an active ingredient to be contained in the drug layer in the film-shaped oral administration preparation produced by the present invention include the following drugs.

Central nervous system drugs (hypnotic sedatives, anxiolytics, antiepileptics, antipyretic analgesics and anti-inflammatory drugs, stimulants, stimulants, anti-angina parkinsonian drugs, mental nerve agents, general cold remedies, etc.), peripheral nervous system drugs (Local anesthetic, skeletal muscle relaxant, autonomic nervous agent, anticonvulsant, etc.), sensory organ drug (ophthalmic drug, antiparasitic agent, etc.), circulatory drug (cardiotonic, arrhythmic, diuretic, blood pressure lowering) Laxatives, vasoconstrictors, vasodilators, agents for hyperlipidemia, etc., drugs for respiratory organs (respiratory stimulants, antitussives, expectorants, bronchodilators, rinsing agents, etc.), drugs for digestive organs (stops) Shiya, intestinal medicine, peptic ulcer, laxative, enema, etc., hormones (salivary gland hormones, thyroid and parathyroid hormones, anabolic steroids, adrenal hormones, estrogen and progestin, Mixed hormonal preparations, urine Reproductive organs and anal drugs (uterine constrictors, contraceptives, hemorrhoids, etc.), dermatological drugs (methoxsalen, etc.), dental and oral drugs (dental antibiotics, etc.), vitamins, nutrient tonics (inorganic drugs) ), Blood and body fluids (anticoagulants), liver disease agents, antidote, gout remedies, sugar sickness agents, cell line drugs, tumor drugs (alkylating agents, antimetabolites) ), Allergic drugs (antihistamines, etc.), crude drugs, herbal medicines, antibiotics, antivirals, anthelmintics, alkaloids (achen alkaloids, coca alkaloids, etc.), non-alkaloids Narcotics (synthetic narcotics such as fenyuyl citrate), etc.

In addition, examples of the active ingredient contained in the drug layer include oral drugs such as quasi-drugs, cosmetics, and health foods having an effect of deodorizing and maintaining health. The coating layer, the drug layer and the support layer used in the film-shaped oral administration agent produced according to the present invention are formed by dissolving or dispersing the above-mentioned components in a solvent as described below, for example, to form an administration agent layer. It is obtained by coating and drying in the process.

Water, ethanol, acetic acid, acetone, anisol, 1-butanol, 2-butano N-butyl acetate, t-butyl methyl ether, cumene, dimethyl sulfoxide, ethyl acetate, getyl ether, ethyl formate, formic acid, heptane, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1- Butanol, methyl ethyl ketone, methyl isobutyl ketone, 2-methyl-1-propanol, pentane, 1-pentanol, 1-propanol, 2-propanol, propyl acetate, tetrahydrolan, acetonitrile, benzene, Mouth form, cyclohexane, 1,2-dichloroethene, dichloromethane, 1,2-dimethoxyethane, N, N-dimethylacetamide, N, N-dimethylformamide, 1,4-dioxane, 2-ethoxyethanol, Ethylene glycol, formamide, hexane, Tanol, 2-methoxyethanol, methylbutylketone, methylcyclohexane, N-methylpyrrolidone, nitromethane, pyridine, sulfolane, tetralin, toluene, 1,1,2-trichloroethene, xylene, 1,1-diethoxypropane 1,1,1-dimethoxymethane, 2,2-dimethyloxypropane, isooctane, isopropyl ether, methyl isopropyl ketone, methyl tetrahydrofuran, petroleum ether, trichloroacetic acid, trifluoroacetic acid, methylene chloride and the like.

In addition, additives such as a plasticizer, a flavoring agent, a flavoring agent, and a coloring agent can be added to the film-shaped oral administration agent produced by the present invention, if necessary. Examples of the flavoring agent include sweeteners such as saccharin, glycyrrhizic acid, sucrose, fructose, and mannitol; refreshing agents such as menthol and heart-strength oil; Can be used. Natural or synthetic fragrances can be used as flavoring agents. As the coloring agent, those used in ordinary preparations such as edible lakes can be used.

Example

An example in which a resin film in which a dosage agent layer having a multilayer structure was formed on one surface by lamination was manufactured, and this was punched and molded by the apparatus of the present invention shown in FIG. 5 to produce a film-shaped oral dosage agent. Although shown below, the present invention is not limited to this.

<Preparation of coating layer preparation liquid> 20.0 parts by weight of pullulan and 5.0 parts by weight of D-sorbitol were added to an appropriate amount of purified water, and the mixture was stirred and dissolved to prepare a coating layer preparation liquid.

To a proper amount of ethanol, 1.5 parts by weight of cis-hycetyl pyridinium salt, 1.5 parts by weight of chlorpheniramine maleate, 4.5 parts by weight of macrogol 400, 2.5 parts by weight of menthol 22.5 parts by weight of polyvinylpyrrolidone K 90 and 59.0 parts by weight of hydroxypropylcellulose were added and dissolved by stirring.Into an appropriate amount of purified water, 3.8 parts by weight of dipotassium glycyrrhizinate, sodium saccharin 0. A solution prepared by adding 5 parts by weight, stirring and dissolving was added, and further stirred and mixed to prepare a drug layer I preparation.

In an appropriate amount of ethanol, 4.5 parts by weight of cetylpyridinium chloride, 4.5 parts by weight of chlorpheniramine maleate, 7.0 parts by weight of tannic acid, 13.5 parts by weight of macrogol 400, 11.5 parts by weight of menthol 7 5 parts by weight, 67.5 parts by weight of Polybierpyrrolidone K90 and 182.0 parts by weight of hydroxypropyl cell mouth are added and dissolved by stirring. To this, 11.2 parts by weight of dipotassium glycyrrhizinate in an appropriate amount of purified water is added. Then, 1.5 parts by weight of saccharin sodium was added, and the mixture was dissolved by stirring. The mixture was further stirred and mixed to prepare a liquid preparation for drug layer 11.

① Coating layer + drug layer I coating

The coating layer preparation solution is applied to the surface of the PET (polyethylene terephthalate) film whose back surface has been subjected to silicone release treatment (the surface that has not been subjected to silicone release treatment) using the coating device 60 shown in Fig. 1, dried, and dried to a thickness of 8 A coating layer of ~ 12 m was formed. The preparation of the drug layer I was further applied on the coating layer of the PET film using the coating apparatus 60 of FIG. 1 to form a drug layer I having a thickness of 55 to 75 microns. Thus, an intermediate product A having a laminated structure of the drug layer, the IZ coating layer, and the PET film was manufactured and wound into a roll.

② Application of drug layer II

The coating device shown in Fig. 1 Applying the preparation of the drug layer II using, and drying to form the drug layer II having a thickness of 55 to 75 m, producing the intermediate product B having a laminated structure of the drug layer II / PET film, and Rolled up.

① 1st process

The intermediate product A and a part of the intermediate product B obtained above are put together using the crimping device 80 of FIG. 2 so that the drug layer I of the intermediate product A and the drug layer II of the intermediate product B face each other. After compression bonding, the PET film of the intermediate product B was peeled off, and an intermediate product C having a laminated structure of the drug layer II / the drug layer IZ coating layer ZPET film was manufactured and wound into a roll.

② 2nd process

The intermediate product C and the remainder of the intermediate product B obtained in the first step above are combined with the drug layer II of the intermediate product C and the intermediate product B using the crimping device 80 in FIG. After pressure bonding with the drug layer II facing, the PET film of the intermediate product B is peeled off, and the intermediate product having the laminated structure of the drug layer II Z drug layer ΠΖ drug layer I / coating layer ZPET film is removed. Manufactured. This intermediate product was divided into two parts, each of which was wound into a roll, to obtain an intermediate product D and an intermediate product D '.

③ Third step

The intermediate product D and the intermediate product D 'having the same configuration and wound into a roll shape obtained in the second step are combined with each other by using a crimping device with the slitter device 90 shown in FIG. 4 functioning. After pressure bonding with the drug layer II facing, the PET film of the intermediate product D was peeled off, passed through a slitter device 90, cut into narrow widths, and wound into reels 33a and 33b, respectively. Was. Thus, coating layer Z drug layer

IZ drug layer Drug layer IIZ drug layer I Coating layer / PET film laminated structure, and a narrowly cut intermediate product E was produced.

The narrow intermediate product E obtained above was laminated using the punching and molding apparatus 10 shown in FIG. 5 with a circular cutting blade 13 having a diameter of 15 mm so as not to reach the back of the PET film. Only the layer was punched out to obtain a circular film lozenge. Industrial applicability

As can be seen from the details described above, according to the method and the apparatus for punching out a film-form oral administration agent of the present invention, the oral administration agent is prevented by preventing the cutting blade from reaching the back surface of the resin film. Only the layer is punched out, and the orally administered agent that has been punched out is peeled off from the resin film by moving while being sucked and held, and then blown out, so that an orally administered agent without a resin film layer can be manufactured. As a result, a final product of an orally administered drug can be obtained without the trouble of peeling off the resin film when administered orally.

In addition, when the oral administration layer is transferred to a punching process or a punching mechanism, the oral administration layer is stretched during the transfer because the oral administration layer is not transferred by the oral administration layer alone but is transferred integrally with the resin film. As a result, there is no thickness unevenness or meandering. In addition, since the remaining drug layer scum after punching the oral drug layer into the prescribed dosage form is also removed in a state integrated with the resin film, it is administered even when it is removed by a winding operation or the like. The agent layer residue can be reliably removed without breaking.

In a preferred embodiment of the method for punching and molding a film-like oral administration agent according to the present invention, two oral administration agent layer-forming resin films formed by applying an oral administration agent layer of the same component or a different component are provided. Are overlapped so that the surfaces of the oral administration agent layers face each other, and pressure is applied from the back surface of the resin film to bring the oral administration agent layers into close contact with each other. Since the film was formed so that only the film was peeled off from the closely adhered intraoral administration layer, a laminated film-shaped intraoral administration layer formed on one side of the resin film was prepared as a formulation layer on a conventional resin film When applying and drying the liquid repeatedly to form the desired number of formulation layers W

Compared with the conventional method, it can be manufactured with high productivity, and the quantitative accuracy required for pharmaceutical preparations and the like can be remarkably improved as compared with the conventional method of layering. In particular, the orally-administered agent layer-forming resin film obtained in the above-mentioned orally-administered agent layer forming step is rolled into a mouth to form a roll film, and the obtained same or different component is administered orally. By unwinding each of the two roll films on which the drug layers are formed, each oral administration agent layer is superimposed on each other so as to face each other and pressed from the back surface of each resin film to form a laminated film in the oral cavity. Dosage can be manufactured in a batch system, making the manufacturing equipment compact and efficiently manufacturing a laminated film-shaped intraoral drug with multiple layers of the desired number of drug layers using the crimping method. It becomes possible.

Further, in a preferred embodiment of the punching / molding apparatus for a film-shaped oral administration agent of the present invention, the punched oral administration agent layer sucked and held by the cutting blade is blown out from the cutting blade by blowing out gas. By disposing a suction pad that adsorbs the blown-out oral administration agent layer at a predetermined position, the oral administration agent layer that is blown out from the cutting blade when the cutting blade and the suction pad approach each other. Is reliably transferred to the suction pad, and is sucked and held by the suction pad, so that transfer to the next process can be performed efficiently.

Claims

Range of request

1. Move the cutting blade that punches out the oral administration agent layer of a predetermined thickness formed on one surface of the resin film into the prescribed dosage form so as not to reach from the oral administration agent layer side to the back surface of the resin film. An orally administered drug layer punching step of punching only the orally administered drug layer into a predetermined dosage form,

At the time of punching, the punched-out oral administration agent layer is sucked and held on the cutting blade side as it is, and is transported while being sucked and held, thereby peeling the punched-out oral administration agent layer from the resin film. Oral administration agent layer suction peeling step,

Blowing out the punched-out oral administration agent layer that has been transferred to a predetermined position in a state of being held by suction, and supplying the next oral administration agent layer to the next step. Punching and molding method of the administration agent.

2. A cutting roll having an annular cutting blade for punching the oral administration agent layer into a predetermined dosage form from a resin film having an oral administration agent layer having a predetermined thickness formed on one surface; While passing through the gap between the anvil roll serving as an anvil and preventing the cutting blade of the cutting roll from reaching the oral administration agent layer side to the back surface of the resin film, only the oral administration agent layer is a predetermined agent. An orally administered drug layer orifice punching step,

A vent opening on the outer surface of the cutting roll body inside the annular shape of the cutting blade until the cutting blade rotates to a predetermined position with the rotation of the cutting roll after the cutting blade punches out the oral administration agent layer. From the above, the punched-out oral administration agent is maintained by suction-holding the punched-out oral administration agent layer inside the annular shape of the cutting blade through an air passage formed inside the cutting roll main body. An oral administration agent layer roll suction peeling step of peeling the layer from the resin film,

When the cutting blade is rotationally moved to the predetermined position, a gas is blown out from the ventilation port through the ventilation path, and the punched-out oral administration agent layer transported while being suction-held is blown out. The orally administered drug layer mouth blowing step to be supplied to the next step.

And a method of punching and molding a film-like oral agent for administration.

3. the orally administered agent layer formed on one surface of the resin film, an orally administered agent layer forming step of applying an orally administered agent layer of a predetermined thickness on the surface of the resin film,

The two intraoral administration agent layer-forming resin films having the same or different components formed in the intraoral administration agent layer formation step obtained in the above-mentioned intraoral administration agent layer forming step are placed such that each oral administration agent layer surface faces each other. An oral administration agent layer pressing step of bringing the oral administration agent layers into close contact with each other by applying pressure from the back surface of the resin film,

3. The method for punching out a film-like intraorally administered agent according to claim 1 or 2, characterized by comprising:

4. the orally administered agent layer formed on one surface of the resin film, an orally administered agent layer formed by applying an orally administered agent layer of a predetermined thickness on the surface of the resin film,

3. The method for punching out a film-form oral administration agent according to claim 1 or 2, wherein the method comprises:

5. Make sure that the cutting blade that punches out the oral administration agent layer of a predetermined thickness formed on one surface of the resin film into the prescribed dosage form does not reach from the oral administration agent layer side to the back surface of the resin film. An orally administered drug layer punching mechanism for punching only the orally administered drug layer into a predetermined dosage form by moving At the time of punching, the punched-out oral administration agent layer is sucked and held on the cutting blade side as it is, and is transported while being suction-held, thereby peeling the punched-out oral administration agent layer from the resin film. Supplying the next oral administration layer by blowing out the punched-out oral administration agent layer that has been transported to a predetermined position while holding it by suction.

A punching and molding apparatus for a film-like oral administration agent, characterized by comprising:

6. A cutting roll having an annular cutting blade for punching the oral administration agent layer of a predetermined thickness formed on one surface of the resin film into a predetermined dosage form, and an anvil roll serving as a metal for the cutting roll, The gap between the cutting roll and the anvil roll is such that the cutting blade of the cutting roll punches out only the oral administration agent layer into a predetermined dosage form without reaching the back surface of the resin film from the oral administration agent layer side. And an adjustment mechanism for adjusting

A vent is opened on the outer surface of the cutting roll body inside the annular shape of the cutting blade, and a ventilation path communicating with the vent is formed along the axial direction inside the cutting roll body, and the cutting blade is used for an intraoral administration agent layer. When the cutting blade rotates to the predetermined position with the rotation of the cutting roll after punching, the air passage is sucked.When the cutting blade rotates to the predetermined position, the air flows through the ventilation passage. An air passage suction / exhaust mechanism for blowing out gas from said vent hole.

7. The method according to claim 5, further comprising a moving mechanism for integrally moving the remaining agent layer from which the oral administration agent layer has been punched and the resin film. Punching device for film-shaped intraoral administration agent.

8. When the cutting blade holding the punched-out oral administration agent layer by suction and rotating to the predetermined position where gas is blown out from the ventilation port, a cutting blade roll inside the cutting blade in an annular shape. A suction pad arranged at a position facing the outer surface of the main body, wherein the blown-out oral administration agent layer is sucked and held by the suction pad and transferred to the next step. Item 8. The punching and molding apparatus for a film-like orally administered agent according to Item 7 or 7.

9. The cutting roll includes a plurality of the annular cutting blades arranged in a circumferential direction. The vents, which are opened on the outer surface of the roll body on the inner side of the annular shape of the cutting blades arranged in the same direction, are individually provided in the individually provided ventilation passages corresponding to the cutting blades arranged in the circumferential direction. 9. The punching and molding apparatus for a film-like oral administration agent according to any one of claims 6 to 8, wherein the apparatus is in communication with the device.

10. The cutting roll has a plurality of the annular cutting blades arranged in the axial direction, and the ventilation port opened to the outer surface of the roll body inside the annular shape of each of the cutting blades arranged in the axial direction has a common shape. 10. The punching and molding apparatus for a film-shaped oral administration agent according to any one of claims 6 to 9, wherein the apparatus is in communication with an air passage.

1 1. A plurality of vents arranged in the circumferential direction are opened on the outer surface of the anvil roll, and a ventilation path communicating with the vent is formed along an axial direction inside the anvil roll, and the resin film is anvil. The film-shaped oral cavity according to any one of claims 6 to 10, wherein a resin film suction mechanism for sucking the air passage is provided while being in contact with the outer surface of the roll. Punching device for internal administration.