JP4606748B2 - Method for producing solid preparation - Google Patents

Description

The present invention relates to a method for producing a solid preparation . More specifically, the drug is not absorbed in the stomach after taking, and the drug is continuously absorbed by adhering to the intestinal wall after the outermost layer is decomposed in the intestine. The present invention relates to a method for producing an enteric solid preparation having the property of being produced .

  In recent years, many drugs with high pharmacological activity have been developed, but peptide antibiotics such as vancomycin and penicillin antibiotics are in the process of reaching the intestine, which is the absorption site in the usual administration method. Because it is degraded or bioavailability is reduced, most of it is discharged from the body without being used.

Conventionally, in order to improve bioavailability by oral administration, a preparation of a two-layer structure in which a drug-containing layer and a poorly water-soluble layer are laminated, or a layer of a bioadhesive substance for adhesion to the digestive tract wall has been provided. Laminated formulations have been developed. And as a manufacturing method of such a solid preparation, after filling a recess made in a film of poorly water-soluble polymer with a drug solution, drug powder, etc., the enteric polymer film is bonded and sealed, There has been proposed a method of obtaining a fine solid preparation by punching with a puncher having a caliber (for example, about 3 mm). (For example, refer to Patent Document 1).
JP 2002-338456 A

  However, the method described in Patent Document 1 has a problem that, when trying to prepare a preparation having a diameter of 150 μm or less, it is difficult to process the end face with high accuracy and a preparation having a good appearance cannot be obtained. .

  The present invention has been made to solve such problems, and an object of the present invention is to provide a method for producing a solid preparation having excellent end face accuracy and good appearance even in a fine preparation having a diameter of 150 μm or less. .

The solid preparation is formed by laminating a bioadhesive layer on one side of the drug layer and laminating a layer made of a poorly water-soluble polymer on the other side and covering the outside of the bioadhesive layer. Is provided with an alkali-soluble layer and has a diameter or a side length of 5 to 150 μm.

1st invention of this invention is a manufacturing method of a solid formulation, and forms the 1st layer which is a bioadhesive layer or a poorly water-soluble polymer layer on a board | substrate directly or through a mold release layer using a spin coater. A step of laminating a drug layer on the first layer using a spin coater, and the first layer of the poorly water-soluble polymer layer or the bioadhesive layer on the drug layer. A layer different from the above is laminated using a spin coater to form a three-layer laminate having a thickness of 3 to 50 μm, and the laminate obtained in the step is irradiated with laser and cut in the XY directions. A step, a step of peeling the laminate cut in the step from the substrate, a laminate particle separated from the substrate and individually divided, and a liquid containing an alkali-soluble polymer, and the outside of each particle A coating layer made of the polymer A method of manufacturing a solid preparation comprising a step of, length of the diameter or side of the solid preparation is characterized in that it is a 5 to 150 m.

A second invention of the present invention is a method for producing a solid preparation, comprising a step of forming a bioadhesive layer on a substrate directly or via a release layer using a spin coater, and a drug on the bioadhesive layer. A step of laminating a layer using a spin coater, a first laser cutting step of irradiating the double layer of the bioadhesive layer and the drug layer with a laser to cut in an XY direction, and the first laser A step of coating a layer made of a poorly water-soluble polymer on the double layer cut in the cutting step using a spin coater, and irradiating the coating layer made of the poorly water-soluble polymer with a laser, the first laser A second laser cutting step of cutting in the XY direction at the same position as the cutting step; a step of peeling the laminate cut in the second laser cutting step from the substrate; The laminated particles Mixed with a liquid comprising a polymer of potash soluble, a method for producing a solid preparation comprising a step of forming a coating layer made of the polymer on the outside of each particle, the length of the diameter or side of the solid dosage 5 ˜150 μm .

A third invention of the present invention is a method for producing a solid preparation, comprising a step of forming a layer comprising an alkali-soluble polymer on a substrate directly or via a release layer using a spin coater, and from the alkali-soluble polymer. forming by using a spin coater bioadhesive layer on the layer comprising the steps of forming by stacking using a spin coater drug layer on the bioadhesive layer, wherein the alkali-soluble polymer layer and the bioadhesive A first laser cutting step of irradiating the triple layer of the layer and the drug layer with a laser to cut in the XY direction, and a layer made of a poorly water-soluble polymer on the triple layer cut in the first laser cutting step a step of coating using a spin coater, a laser is irradiated to the coating layer made of the flame aqueous polymer, a second laser for cutting the XY direction at the same position as the first laser cutting process The cross-sectional step, the cut laminate the second laser cutting process method for manufacturing a solid preparation comprising a step of peeling from the substrate, the length of the diameter or side of the solid dosage 5~150μm It is characterized by being.

  According to the present invention, a laminate formed by laminating at least a drug layer, a bioadhesive layer, and an alkali-soluble polymer layer is cut into a grid pattern in the X and Y directions by irradiating a laser, and thereby punching or the like. Compared with the conventional cutting method, the processing dimension can be significantly reduced. In addition, a solid preparation having an extremely fine and asymmetric laminated structure and excellent end face accuracy and good appearance can be obtained.

  Hereinafter, embodiments of the present invention will be described.

FIG. 1 is a cross-sectional view showing a first embodiment of a solid preparation . In the figure, reference numeral 1 denotes a drug layer, and a barrier layer 2 and a bioadhesive layer 3 made of a poorly water-soluble polymer are respectively laminated on both sides of the drug layer 1. In addition, an alkali-soluble layer 4 which is an enteric layer is provided on the outside of the laminate in which the barrier layer 2, the drug layer 1 and the bioadhesive layer 3 are thus laminated. It has a very small diameter (or side) of ˜150 μm.

  The drug layer 1 is a layer that contains a water-soluble polymer as a main base component and contains a drug. Examples of the water-soluble polymer include methyl cellulose, carboxymethyl cellulose and salts thereof, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl alcohol, polyethylene glycol, polyethylene oxide and the like. These may be used alone or as a mixture of two or more.

  Drugs include water-soluble, low-absorbency drugs (aminoglycoside antibiotics, penicillin antibiotics, cephalosporin antibiotics, cephem antibiotics, peptide antibiotics, antiviral drugs such as acyclovir, epirubicin, etc. And various drugs including peptide and peptide drugs such as insulin, calcitonin, various interferons, growth hormone, vasopressin and derivatives thereof.

  The barrier layer 2 is composed of a poorly water-soluble polymer that is stable to gastric acid and other digestive fluids. Examples of poorly water-soluble polymers include poorly soluble cellulose such as ethyl cellulose, cellulose acetate propionate, and cellulose acetate butyrate, and higher fatty acids such as hydroxypropyl cellulose phthalate, cellulose acetate phthalate, shellac, palmitic acid, and stearic acid. It is done.

  The bioadhesive layer 3 contains a bioadhesive substance that inactivates the activity of digestive enzymes present in the small intestinal mucosa and adheres to the absorbing cells of the digestive tract (small intestine in this case) wall. By increasing the concentration gradient of drug molecules between the mucosa and cells for a long time, high absorption efficiency is achieved.

  Bioadhesive substances include sodium alginate, pullulan, pectin, tragacanth, gum arabic, acidic polysaccharides or salts thereof, carboxyvinyl polymer, polyacrylic acid such as sodium polyacrylate or salts thereof, acrylic acid copolymer or Examples thereof include cellulose derivatives such as salts, carboxymethyl cellulose and sodium salts.

  In order to further enhance the drug absorption effect, the bioadhesive layer 3 can contain an absorption promoter. When an absorption enhancer is used in combination, the drug and the absorption enhancer always coexist in a limited closed space, so that the effect can be maximized. Examples of the absorption accelerator include Labrasol TM and sodium caprate.

  The alkali-soluble layer 4, which is an enteric layer, dissolves only when it reaches the most advantageous pH (alkaline, which is the pH in the small intestine) for absorption of the drug, and prevents the drug from being decomposed by gastric acid or the like until then. . The alkali-soluble layer 4 is made of an alkali-soluble polymer that is stable against gastric acid.

  Examples of alkali-soluble polymers include cellulose acetate trimellitate, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose (CMEC), methacrylic acid-acrylic acid ethyl ester copolymer, methacrylic acid -Methacrylic acid methyl ester copolymer. These are used alone or in combination of two or more.

  The alkali-soluble layer 4 is desirably formed so as to cover at least the outer side of the bioadhesive layer 3. Although it is not always necessary to cover the barrier layer 2, it is advantageous to form it so as to cover the entire outer periphery of the preparation because an efficient production method described later can be adopted.

  In the structure in which the alkali-soluble layer 4 is formed so as to cover the entire outer periphery of the preparation, the barrier layer 2 is not necessarily required, but the alkali-soluble layer 4 dissolves in the intestine, and the bioadhesive layer 3 forms the small intestine. The barrier layer 2 functions to protect the drug from an attack such as digestive fluid while the drug is continuously injected into the cell while attached to the cell. Therefore, the lowering of the medicinal effect is less when the barrier layer 2 is provided.

  Next, a method for producing a solid preparation having such a structure will be described with reference to the drawings.

  In the first embodiment of the manufacturing method, as shown in FIG. 2 (a), it is difficult to form on a substrate 5 such as silicon or glass coated with a release agent (not shown) as necessary. After the barrier layer 2 made of a water-soluble polymer is formed, the drug layer 1 is formed thereon.

  In order to form these layers, a solution containing a sparingly water-soluble polymer or a solution containing a drug containing a water-soluble polymer as a base component is applied using a coating device such as a spin coater, bar coater, or die coater. After coating, a method of heating and drying is employed. Since a thin layer can be formed, application by a spin coater is most preferable. The heating and drying conditions are preferably heating at a temperature of 50 to 80 ° C. for 5 to 10 minutes.

  Next, as shown in FIG. 2 (b), a solution containing a bioadhesive substance is applied onto the drug layer 1 using an application device such as a spin coater, bar coater, or die coater, and then 50-80. The bioadhesive layer 3 is formed by heating and drying at a temperature of 5 ° C. for 5 to 10 minutes. Thus, a three-layer laminated film having a thickness of about 3 to 50 μm is obtained.

  Next, as shown in FIG. 2C, the three-layer laminated film is irradiated with a laser 6 and cut in the XY directions. In this way, the laminated film is cut into a grid of several μm to several tens of μm square. Cutting by irradiation with the laser 6 has advantages such as a narrow processing width, a small cutting allowance (width of a kerf), no cutting strain around, and a high cutting speed.

  As the laser, it is desirable to use a laser having an oscillation wavelength (λ) of 190 to 600 nm. Specifically, an XeF excimer laser (λ = 351 nm), an XeCl excimer laser (λ = 308 nm), a KrF excimer laser (λ = 248 nm), or an ArF excimer laser (λ = 193 nm) can be used. Furthermore, Ar laser + SHG (second harmonic) (λ = 257 nm), YAG laser + 5HG (fifth harmonic) (λ = 213 nm), YAG laser + FHG (fourth harmonic) (λ = 266 nm), YAG laser + THG A harmonic laser such as (third harmonic) (λ = 355 nm) can also be used. By using such an ultraviolet laser, the processing accuracy of the cut end surface can be increased, and a smooth end surface with good dimensional accuracy can be obtained.

  Next, as shown in FIG. 2D, the laminated film in which the kerf 7 is formed is peeled off from the substrate 5 and divided into individual pieces, and then divided into granular laminates as shown in FIG. The body 8 is added to and mixed with the liquid 9 containing the alkali-soluble polymer, and a coating layer made of the alkali-soluble polymer is formed on the entire outer periphery of each laminate 8.

  In this way, the solid preparation shown in FIG. 1 is obtained. This solid preparation has a very small diameter of several μm to several tens of μm, is excellent in end face accuracy of the laminate 8 as a core, and has a good appearance. In the manufacturing method of the first embodiment, the order of the steps of forming the barrier layer 2 and the bioadhesive layer 3 is reversed, and the bioadhesive layer 3, the drug layer 1, and the barrier layer 2 are formed in this order. The same effect can be achieved.

  A second embodiment of the production method of the present invention will be described. In this embodiment, as shown in FIG. 3 (a), the bioadhesive layer 3 and the drug layer 1 are formed on the substrate 5 in the same manner as in the first embodiment, and then in FIG. 3 (b). As shown, the two-layer laminated film of the bioadhesive layer 3 and the drug layer 1 is irradiated with a laser 6 and cut into a grid pattern of several μm to several tens μm square in the XY direction.

  Next, as shown in FIG. 3 (c), a solution containing a poorly water-soluble polymer as a barrier material is applied onto the cut two-layer laminated film using a coating device such as a spin coater, a bar coater, or a die coater. After coating, the barrier layer 2 is formed by heating and drying. Thus, the barrier layer 2 is continuously formed so as to cover the entire outer periphery of the two-layer laminated film including the inside of the kerf 7a.

  Next, as shown in FIG. 3D, the barrier layer 2 is irradiated with a laser 6 to cut the bioadhesive layer 3 at the same position as the kerf 7a of the two-layer laminated film.

  Next, the laminated film thus formed with the new kerf 7b was peeled off from the substrate 5 and divided into individual pieces as shown in FIG. 3 (e), and then divided as shown in FIG. 3 (f). The laminated body 8 is added and mixed in the liquid 9 containing an alkali-soluble polymer, and the coating layer which consists of an alkali-soluble polymer is formed in the whole outer periphery of each laminated body 8. FIG.

  The solid preparation thus obtained is shown in FIG. This solid preparation has a very small diameter of several μm to several tens of μm, is excellent in end face accuracy of the laminate 8 as a core, and has a good appearance. In addition, since the barrier layer 2 is formed not only on the drug layer 1 but also covers the end face of the two-layer laminated film of the bioadhesive layer 3 and the drug layer 1, the barrier layer 2 is obtained by the first embodiment. Compared to a solid preparation, there is an advantage that there is less leakage of the drug from the end face.

  A third embodiment of the manufacturing method of the present invention will be described. In this embodiment, as shown in FIG. 5 (a), the alkali-soluble layer 4, the bioadhesive layer 3 and the drug layer 1 are sequentially formed on the substrate 5 via a release layer (not shown). After that, as shown in FIG. 5B, the laser 6 is irradiated and cut into a grid pattern of several μm to several tens of μm square in the XY direction. Reference numeral 10a denotes a kerf.

  Next, as shown in FIG. 5 (c), a solution containing a poorly water-soluble polymer as a barrier material is applied onto the cut three-layer laminated film using a coating device such as a spin coater, a bar coater, or a die coater. After coating, the barrier layer 2 is formed by heating and drying. In this way, the barrier layer 2 is continuously formed so as to cover the entire outer periphery of the three-layer laminated film including the cut groove 10a.

  Next, as shown in FIG. 5D, the barrier layer 2 is irradiated with a laser 6 to cut the barrier layer 2 at the same position as the cut groove 10a of the three-layer laminated film.

  Next, the laminated film thus formed with the new kerf 10b is peeled off from the substrate 5 and divided into individual pieces as shown in FIG. The solid preparation thus obtained is shown in FIG.

  In this solid preparation, since the cut end surface of the drug layer 1 is covered with the barrier layer 2 and the lower surface is the alkali-soluble layer 4, compared with the solid preparation obtained by the first embodiment. There is little leakage of drug from the end face. Further, there is an advantage that the manufacturing process is simple as compared with the first and second embodiments.

  Hereinafter, the present invention will be described in detail with reference to examples. In addition, these Examples do not limit the scope of the present invention.

Example 1
Using a spin coater, a toluene-ethanol (80:20) solution of ethyl cellulose, which is a poorly water-soluble polymer (concentration: 14% by weight), is applied onto a silicon substrate coated with a silicone release agent (dimethylpolysiloxane). After coating, it was dried by heating at 80 ° C. for 5 minutes. The film thickness after drying was 8 μm.

  Next, a polyvinyl alcohol solution of insulin blended with sodium caprate as an absorption accelerator was applied onto the obtained dried film using a spin coater, and left in a freezer for 1 hour to freeze the insulin solution. Next, an aqueous solution of sodium alginate, a bioadhesive substance (concentration 3% by weight), was applied onto the frozen insulin solution using a spin coater, and then allowed to stand for 2 nights while sending air under low temperature. The solvent was distilled off.

  The three-layered film thus obtained was irradiated with ArF excimer laser (λ = 193 nm) from the upper surface and cut into a 30 μm square grid pattern. Next, the cut laminated film is peeled off from the silicon substrate and divided from the cut groove, and then the divided granular laminate is mixed with ethyl acetate-isopropanol (80:20) of cellulose acetate trimellitate which is an alkali-soluble polymer. It was added in the solution (concentration 11% by weight). And it mixed, stirring with a mechanical stirrer, and dried, and the coating layer of the cellulose acetate trimellitate was formed in the outermost layer.

  Thus, a solid preparation having a diameter of 36 μm, excellent end face accuracy and good appearance was obtained.

Example 2
In the same manner as in Example 1, after forming a dry film of ethyl cellulose (film thickness: 8 μm) on a silicon substrate, an insulin solution containing polyvinyl alcohol as a base material and sodium caprate is formed thereon using a spin coater. It was applied and left in the freezer for 1 hour to freeze the insulin solution. Next, a 3% by weight aqueous sodium alginate solution was applied onto the frozen insulin solution in the same manner as in Example 1, and then the solvent was distilled off.

  Next, the obtained three-layer laminated film was irradiated with an ArF excimer laser (λ = 193 nm) from the upper surface, and cut into a 30 μm square grid pattern. Next, after the cut laminated film was peeled from the silicon substrate, it was added to the cellulose acetate trimellitate solution in the same manner as in Example 1, and stirred and mixed. Thereafter, it was dried to form a coating layer of cellulose acetate trimellitate on the outermost layer.

  Thus, a solid preparation having a diameter of 36 μm, excellent end face accuracy and good appearance was obtained.

Example 3
A 3% by weight sodium alginate aqueous solution was applied on a silicon substrate coated with a release agent using a spin coater, and then left to stand for 2 nights while feeding air at a low temperature to distill off the solvent.

  Next, an insulin solution containing hydroxypropylcellulose as a base material and sodium caprate as an absorption accelerator was applied thereon using a spin coater, and left in a freezer for 1 hour to freeze the insulin solution.

  Next, the obtained two-layer structure film was irradiated with ArF excimer laser (λ = 193 nm) and cut into a 30 μm square grid. Thereafter, a dry film of ethyl cellulose which is a poorly water-soluble polymer was formed thereon. The film thickness after drying was 18 μm.

  Next, ArF excimer laser (λ = 193 nm) was irradiated again from above the ethylcellulose layer thus obtained, and a kerf was formed at the same position as the previous kerf. Thus, the laminated film in which the ethylcellulose layer was coated on the two-layer structure film was cut into a 30 μm square grid pattern. Next, after the laminated film thus cut again is peeled off from the silicon substrate and divided from the kerf, the divided laminated body is made of toluene-ethanol (80:20 of hydroxypropylmethylcellulose phthalate which is an alkali-soluble polymer). ) It was added to the mixed solution (concentration 11 wt%). And it mixed, stirring with a mechanical stirrer, and dried, and the coating layer of the hydroxypropyl methylcellulose phthalate was formed in the outermost layer.

  Thus, a solid preparation having a diameter of 36 μm, excellent end face accuracy and good appearance was obtained. This solid preparation has the advantage that there is less drug leakage from the end face than the preparations obtained in Examples 1 and 2 because the cut end face of the drug layer is covered with an ethyl cellulose layer which is a barrier layer. It was.

Example 4
After applying a toluene-ethanol (80:20) mixed solution (concentration: 11% by weight) of hydroxypropylmethylcellulose phthalate, which is an alkali-soluble polymer, on a silicon substrate coated with a release agent using a spin coater, it is dried. A hydroxypropyl methylcellulose phthalate layer was formed.

  Next, a 3% by weight sodium alginate aqueous solution was applied thereon using a spin coater, and then left to stand for 2 nights while feeding air at a low temperature to distill off the solvent.

  Next, an insulin solution containing hydroxypropylcellulose as a base material and sodium caprate as an absorption accelerator was applied thereon using a spin coater, and left in a freezer for 1 hour to freeze the insulin solution.

  The three-layer structure film thus obtained was irradiated with an ArF excimer laser (λ = 193 nm) and cut into a 30 μm square grid. Thereafter, a dry film of ethyl cellulose which is a poorly water-soluble polymer was formed thereon. The film thickness after drying was 21 μm.

  Next, ArF excimer laser (λ = 193 nm) was irradiated again from above the ethyl cellulose layer, and a kerf was formed at the same position as the previous kerf. Thus, the laminated film in which the ethylcellulose layer was coated on the three-layer structure film was cut into a 30 μm square grid pattern. Next, the laminated film that had been cut again was peeled from the silicon substrate and divided from the cut grooves.

  Thus, a solid preparation having a diameter of 30 μm, excellent end face accuracy and good appearance was obtained. In this solid preparation, the cut end surface of the drug layer is covered with an ethyl cellulose layer which is a barrier layer, and the lower surface is an alkali-soluble layer, so that it is compared with the preparations obtained in Examples 1 and 2. There was an advantage that there was little leakage of the drug from the end face, and the manufacturing process was simple compared to Examples 1-3.

  According to the present invention, it is possible to obtain a solid preparation having a very fine and asymmetric laminated structure, excellent end face accuracy and good appearance. Therefore, according to this solid preparation, genetically engineered protein drugs, polymer drugs, water-soluble difficult / low absorbable drugs (aminoglycoside antibiotics, penicillin antibiotics, cephalosporin antibiotics, cephem antibiotics, The absorption rate after oral administration of peptide antibiotics, antiviral drugs, anticancer drugs, etc.) can be greatly increased.

It is sectional drawing which shows 1st Embodiment of a solid formulation . It is sectional drawing for demonstrating 1st Embodiment of the method of manufacturing a solid formulation. It is sectional drawing for demonstrating 2nd Embodiment of the method of manufacturing a solid formulation. It is sectional drawing which shows the structure of the solid formulation manufactured by 2nd Embodiment. It is sectional drawing for demonstrating 3rd Embodiment of the method of manufacturing a solid formulation. It is sectional drawing which shows the structure of the solid formulation manufactured by 3rd Embodiment.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Drug layer, 2 ... Barrier layer, 3 ... Bioadhesion layer, 4 ... Alkali soluble layer, 6 ... Laser, 8 ... Laminated body, 9 ... Liquid containing alkali-soluble polymer.

Claims (4)

Forming a first layer which is a bioadhesive layer or a poorly water-soluble polymer layer on a substrate directly or via a release layer using a spin coater ;
Forming a drug layer on the first layer by using a spin coater ;
A layer different from the first layer among the poorly water-soluble polymer layer or the bioadhesive layer is laminated on the drug layer by using a spin coater to form a three-layer laminate having a thickness of 3 to 50 μm. Process,
Irradiating the laminated body obtained in the above step with a laser and cutting in the XY direction;
Peeling the laminate cut in the step from the substrate;
A method for producing a solid preparation comprising a step of mixing laminate particles separated from the substrate and individually divided with a liquid containing an alkali-soluble polymer, and forming a coating layer made of the polymer on the outside of each particle. There,
A method for producing a solid preparation, wherein the solid preparation has a diameter or side length of 5 to 150 µm . Forming a bioadhesive layer on a substrate directly or via a release layer using a spin coater ;
Forming a drug layer on the bioadhesive layer by laminating using a spin coater ;
A first laser cutting step in which a double layer of the bioadhesive layer and the drug layer is irradiated with a laser and cut in the XY direction;
Coating the layer composed of a poorly water-soluble polymer on the double layer cut in the first laser cutting step using a spin coater ;
A second laser cutting step of irradiating the coating layer made of the poorly water-soluble polymer with a laser, and cutting in the XY direction at the same position as the first laser cutting step;
Peeling the laminate cut in the second laser cutting step from the substrate;
A method for producing a solid preparation comprising a step of mixing laminate particles separated from the substrate and individually divided with a liquid containing an alkali-soluble polymer, and forming a coating layer made of the polymer on the outside of each particle. There,
A method for producing a solid preparation, wherein the solid preparation has a diameter or side length of 5 to 150 µm . Forming a layer of an alkali-soluble polymer on a substrate directly or via a release layer using a spin coater ;
Forming a bioadhesive layer on the layer made of the alkali-soluble polymer using a spin coater ;
Forming a drug layer on the bioadhesive layer by laminating using a spin coater ;
A first laser cutting step of irradiating the triple layer of the alkali-soluble polymer layer, the bioadhesive layer, and the drug layer with a laser to cut in a XY direction;
A step of coating a layer made of a non-water-soluble polymer on the triple layer cut in the first laser cutting step using a spin coater ;
A second laser cutting step of irradiating the coating layer made of the poorly water-soluble polymer with a laser and cutting in the XY direction at the same position as the first laser cutting step;
A method for producing a solid preparation comprising a step of peeling the laminate cut in the second laser cutting step from the substrate ,
A method for producing a solid preparation, wherein the solid preparation has a diameter or side length of 5 to 150 µm . The method for producing a solid preparation according to any one of claims 1 to 3 , wherein the laser is a laser having an oscillation wavelength of 190 to 600 nm.

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