TWI231760B - Coated lozenge and manufacturing method thereof - Google Patents

Abstract

A preparatory heating is carried out on raw lozenges containing hygroscopic polymer as the primary ingredient in the condition that thermal expansion of the raw lozenges is not entirely lost, which is used to repair roughness on the surface of the raw lozenges at the early stage of the coating by sufficient expansion of the raw lozenges through heating during and after coating liquid application so that coated lozenges with excellent surface smoothness are obtained. When coating process is performed on raw lozenges formed by hygroscopic polymer to produce coated lozenges, the applied coating solution diffuses on the entire surface of the lozenges, which reduces surface strength of the lozenges and thus creates surface roughness of the lozenges at the early stage of the coating; this leads to impaired appearance of the coated lozenges and uneven coated film thickness, which can be overcome by the present invention.

Description

1231760 Μ _________ Β7 V. Description of the invention (1) Name of the technical field of Z (please read the precautions on the back before filling this page) The present invention relates to a method for manufacturing coated tablets with hygroscopic polymers as the main component In particular, it relates to a method for manufacturing a film-coated tablet. In addition, it also relates to a coated tablet obtained by the manufacturing method. Prior art In the past, as a method for manufacturing a coated tablet containing a hygroscopic polymer as a main component, there are known a film coating method and a sugar coating method. The film coating method is, for example, a method in which anion exchange resin is known to contain a certain amount of water, a tablet obtained by tabletting, and then coated with a coating solution containing hydroxypropyl cellulose, etc. 6-1 57325). In addition, a method of adding 14 to 20% by weight of water and 2% by weight or less of silicon dioxide element tablets to an anion exchange resin and coating with a coating solution containing hydroxypropyl methylcellulose or the like (specially Kaiping 7-97330). However, these methods, because a certain amount of water must be contained in the plain tablets, cause a problem that the strength of the tablets is reduced. In addition, it is also known that in the anion exchange resin, no water is added, and a mixture of silicon dioxide and crystalline cellulose is added. A method for spray-coating a coating liquid such as propylmethylcellulose (Japanese Patent Application Laid-Open No. 9-202732, Japanese Patent Application Laid-Open No. 10-11661). In addition, as for tablets containing a hygroscopic high polymer (polyallylamine polymer), as shown in JP-A No. 10-330269 (International Publication No. W098 / 44933) or International Publication No. WO00 / 22008, there are The two are coated with a film, which can also be recorded as a film ingot, especially the latter also records that this paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) -5- 1231760 Employees ’Intellectual Property Bureau of the Ministry of Economic Affairs Cooperative printed A7 B7 V. Description of the invention (2) An example of actually manufacturing a film tablet using a commercially available coating machine. However, when coating tablets of hygroscopic polymers such as polyallylamine-based polymers with the method described above, the film-forming agent solution spreads on the surface of the tablets, causing the surface strength of the tablets to decrease, resulting in At the initial stage of the coating, the surface of the lozenge is rough, which damages the appearance, makes the film thickness uneven, and fails to obtain the intended film function. The present invention aims to provide a method for manufacturing a coated tablet having excellent smoothness on the surface of the tablet, uniform coating, and a hygroscopic polymer as a main component, and particularly to a method for manufacturing a film tablet. In addition, the purpose is to provide a coated tablet having a smooth surface. SUMMARY OF THE INVENTION In view of the above-mentioned problems, the present inventors and others have made intensive research, and obtained a vegetarian tablet containing 50% or more of a hygroscopic polymer under conditions that do not completely lose the thermal expansion energy of the tablet (that is, (At least the condition that the thermal expansion energy of the plain tablet is still partially remaining), preheating is performed, and secondly, when coating the coating liquid or after coating, the tablet is heated to expand thermally, and it can be found that it can be repaired on the surface of the tablet in the early stage of coating Rough, and complete the present invention. Brief Description of the Drawings Figure 1 is an example of a graph showing the increase in thickness of the plain ingot obtained in Example 1 at various temperatures over time. Fig. 2 is a graph showing an example of a graph of a change in thickness of a plain ingot (a moisture content of 5.5 S amount%) 'obtained in the heating example 丨 with time. This paper size applies to China National Standard (CNS) A * size (2i〇X 297 mm) (Please read the precautions on the back before filling this page)

-6-Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 1231760 A7 _ B7 V. Description of the invention (3) Figure 3 shows the plain ingot obtained by heating Example 2 (moisture content is 3.0% by weight), and its thickness is increased. An example of a graph of a quantity over time. FIG. 4 is a graph showing an example of a graph of a change in the thickness of a vegetarian tablet obtained by heating Example 2 with a moisture content of 3.8% by weight over time. FIG. 5 is an example of a graph showing a change in the thickness increase amount of the vegetarian tablet (water content: 8.0% by weight) obtained in Example 3 with time. Fig. 6 is an example of a top view photograph of the appearance of a coated tablet manufactured in Example 4. Fig. 7 is an example of a side photograph showing the appearance of a coated tablet manufactured in Example 4. Fig. 8 is an example of a top view photograph of the appearance of a coated tablet manufactured in Example 5. Fig. 9 is an example of a top view photograph of the appearance of a coated tablet produced in Comparative Example 1. Figs. FIG. 10 is an example of a side photograph showing the appearance of a coated tablet produced in Comparative Example 1. FIG. In the present invention, a veggie tablet containing 50% by weight or more of a hygroscopic polymer is targeted. Although such a plain ingot has thermal expansion energy, if it is heated sufficiently, it will completely lose its original thermal expansion energy. That is, the present invention is to perform pre-heating under such conditions that the thermal expansion energy of the vegetarian ingot is not completely lost (that is, at least the thermal expansion energy of the vegetarian ingot is still partially retained), and then, When coating liquid is applied or after coating, the condition of the tablet is maintained under the condition that the tablet is fully inflated, and the surface condition of the tablet is repaired. This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read first (Notes on the back then fill out this page)

-7- 1231760 A7 _______B7 V. Explanation of the invention (4) on the manufacturing method of coated tablets with hygroscopic polymer as the main ingredient 〇 In addition, the present invention also relates to the coated tablets obtained by the above manufacturing method ( Please read the notes on the back before filling this page). In the present invention, the term "coating" refers to a known coating method generally applicable to tablet coating, such as film coating, sugar coating, and the like, among which film coating is preferred. That is, it is preferable to use a film-coated tablet as the coated tablet. In the present invention, the so-called absorbent polymer means that at a room temperature (22 to 28 ° C) with a relative humidity of 50%, the moisture content becomes as high as 10% by weight or more within one week. molecule. Intellectual Property Bureau of the Ministry of Economic Affairs (industrial and consumer cooperatives printed such hygroscopic polymers, such as acrylic polymers (acrylic acid-vinyl alcohol polymers), methacrylic polymers, acrylamide polymers, olefins Polymers such as propylamine-based polymers, carboxymethylcellulose-based polymers, and biopolymers produced by using fructose as a carbon source also include these salts, silicides, and hydrolysates. In addition, the aforementioned polymers In addition to the respective polymers of the same type, copolymers of these or each of these monomers and copolymers of other monomers that can be copolymerized with these or cross-linkable polymers are also included. Such copolymers can be arbitrarily polymerized It can also be a block polymer or a cross-linked polymer. In addition, it also includes cross-linked products of various polymers prepared by various methods using various cross-linking agents. As the above-mentioned cross-linking agents, multivalent Allyl compounds, polyvalent vinyl compounds, polyvalent epoxy compounds, halogenated epoxy compounds, polyvalent alcohols, polyvalent amines, and vinylidene compounds. As copolymerizable monomers, for example, hydroxyl Ethyl (a ） Acrylic acid, this paper size applies Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm) -8-1231760 Α7 Β7 5. Description of the invention (5) (methoxy) polyethylene glycol (meth) acrylic acid, Alkyl (meth) acrylic acid such as glycerol (meth) acrylic acid and glycosyl ethyl (meth) acrylic acid; N'N-dimethylacrylamide-based and acrylamide-based compounds ; Carboxylic acid compounds such as maleic acid and its metal salts, itaconic acid and its metal salts; 2-acrylamido-2-methylpropanesulfonic acid and its metal salts, vinylsulfonic acid and its metal salts, etc. Sulfonic acid compounds; others such as N-vinylpyrrolidone, etc. In addition, polymers that can be cross-linked with (meth) acrylic acid include hydrophilic properties such as starch, Carrageenan, agarose, and carboxymethyl cellulose. Polysaccharides, etc. Representative cross-linking agents are shown below. Polyvalent allyls: N, N-diallyl acrylamide and N, N-diallyl methacrylamide (these They are all expressed as "N, N-diallyl (meth) acrylamide", the same applies hereinafter), diallyl Polyvalent allylic compounds such as amines, diallyl methacrylamine, diallyl phthalic acid, diallyl maleic acid, etc. Polyvalent vinyls: divinylbenzene, methylidene Ν, Ν '-bis (meth) acrylamide, ethylene glycol di (fluorenyl) acrylic acid, and polyethylene glycol acrylic acid (these are all represented by "(poly) ethylene glycol di (meth) acrylic acid" "below All are the same), (poly) propylene glycol di (meth) acrylic acid and trimethylolpropane triacrylic acid, etc. Polyvalent vinyl compounds. Polyvalent epoxy: (poly) ethylene glycol diglycidyl ester, ( (Poly) propylene glycol diglycidyl ester, glycerol- 1,3-diglycidyl ester, trimethylolpropane triglycidyl ester and (poly) glycerol polyglycidyl acid. This paper applies Chinese National Standards (CNS) Α4 specification (210 × 297 mm) Handling clothes-(Please read the precautions on the back before filling this page) Order printed by the 8th Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs -9-12760 Cooperative printed A7 B7 V. Description of the invention (6) Polycyclic rings of esters, etc. Oxygen compound. Halogenated epoxy: epichlorohydrin, ^ -methylchloropropane, etc. Polyvalent alcohols: (poly) glycerin, (poly) ethylene glycol, trimethylolpropane and pentaerythritol. Polyvalent amines: ethylenediamine, etc. As the hygroscopic polymer used in the present invention, a polyallylamine-based water-absorbing polymer is preferable, and a water-absorbing polymer obtained by cross-linking and polymerizing polyallylamine with epichlorohydrin is also suitable, especially A water-absorbing polymer represented by the following formula (1) [wherein the molar ratio of (a + b): c is 45: 1 to 2: 1: m is an integer] is preferable. The water-absorbing polymer represented by the formula (1) can be prepared according to the method described in Japanese Patent Publication No. 9-5047 82 (International Publication No. WO95 / 05 1 84) or the method described in International Publication No. WO00 / 22008. Got it.

This paper size applies to China National Standard (CNS) A4 (210X 297 mm) (Please read the precautions on the back before filling this page)

-10- 1231760 Α7 B7 V. Description of the invention (7) In addition, as the hygroscopic polymer used in the present invention, the following polymers (2) to (9) are also suitable. -------- Clothing II (Please read the precautions on the back before filling out this page) The polymer (2) is a polymer having the characteristics of a repeating unit as shown by the following formula, or a copolymer thereof. In the formula, 'n is an integer, and R is an independent alkyl group or a lower alkyl group (for example, an alkyl group having 1 to 5 carbon atoms), and an alkylamino group (such as an ethylamine group having 1 to 5 carbon atoms) ) Or aryl (for example, aryl containing 1 to 12 carbon atoms (such as phenyl and naphthyl)).

Printed by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. The polymer (3) is a polymer characterized by repeated units as shown in the following formula, or a copolymer thereof. In the formula, η is an integer, and R is an independent fluorene or a lower alkyl group (for example, an alkyl group containing 1 to 5 carbon atoms), and an alkylamino group (such as an ethylamine group containing 1 to 5 carbon atoms) ) Or aryl (for example, aryl containing 1 to 12 carbon atoms (such as phenyl and naphthyl, etc.)), χ_ is a negatively-charged ion pair that can be exchanged, respectively. R X '

η An example of the copolymer of the above polymer (3) has the following formula: The paper size is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) -11-1231760

X '

Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (8) ⑶ [where η is an integer and R is an independent Η or lower alkyl group (for example, an alkane containing 1 to 5 carbon atoms) Group), alkylamino groups (such as ethylamino groups having 1 to 5 carbon atoms) or aryl groups (such as aryl groups containing 1 to 12 carbon atoms (such as phenyl and naphthyl)), X — is the first repeatable unit represented by the exchangeable negatively charged ion pair], and as shown in the following formula ⑷ [where η is an integer and R is an independent Η or a lower alkyl group (for example, containing 1 Alkyl groups of 5 to 5 carbon atoms), alkylamino groups (such as ethylamino groups of 1 to 5 carbon atoms) or aryl groups (such as aryl groups of 1 to 12 carbon atoms (such as phenyl And naphthyl, etc.))] is a polymer (Polymer (4)) characterized by the second repeating unit. The polymer (5) is a polymer having a repeating unit represented by the following formula, or a copolymer thereof. In the formula, η is an integer, R is Η or a lower alkyl group (for example, an alkyl group containing 1 to 5 carbon atoms), an alkylamino group (such as an ethylamino group having an alkylamine group having 1 to 5 carbon atoms), or Aromatic (for example, containing 1 paper size applicable to the Chinese National Standard (CNS) A4 size (210X 297 mm) (Please read the precautions on the back before filling out this page)

-12- r η Printed by the 8th Industrial Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 1231760 A7 B7 V. Description of the invention (9) Aromatic groups (such as phenyl and naphthyl) of 12 carbon atoms ⑸

R Another example of the copolymer of the above polymer (3) has the following formula:

R

[In the formula, η is an integer, R is Η or a lower alkyl group (for example, an alkyl group having 1 to 5 carbon atoms), and an alkylamino group (such as an ethylamino group having an alkylamino group having 1 to 5 carbon atoms) Or an aryl group (for example, an aryl group containing 1 to 12 carbon atoms (such as phenyl, naphthyl, etc.))] and the first repeating unit represented by the formula X '1 / ⑹

R

[In the formula, 11 is an independent integer, R is fluorene or a lower alkyl group (for example, an alkyl group containing 1 to 5 carbon atoms), and an alkylamino group (such as an ethylamine group containing 1 to 5 carbon atoms) Amine group) or aryl group (such as aryl groups containing 1 to 12 carbon atoms (such as phenyl and naphthyl, etc.))] The second repeating unit indicated in this paper applies Chinese National Standard (CNS) A4 specifications （210 乂 297mm） (Please read the notes on the back and save this page)

-13- 1231760 Printed by A7 B7, Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention (1 () polymer (Polymer (6)). The polymer (7) has the following formula: Polymers characterized by repeated units, or copolymers thereof. In the formula, n is an integer 'R1 and R2 are independent fluorene or lower radicals (for example, radicals containing 1 to 5 carbon atoms), alkylamine groups (Such as an ethylamino group containing 1 to 5 carbon atoms) or an aryl group (such as an aryl group containing 1 to 12 carbon atoms (such as phenyl, naphthyl, etc.)), X_ is respectively interchangeable Negatively charged ion pairs.

X

Among the aforementioned polymers (7), a suitable polymer is a polymer in which at least one R! Or R2 in the formula is hydrogen. The polymer (8) is a polymer having a repeating unit, or a copolymer thereof, as represented by the following formula. In the formula, η is an integer, Ri and R2 are independent fluorene or alkyl and alkylamino groups containing 1 to 20 carbon atoms (such as ethylamino alkylamino groups containing 1 to 5 carbon atoms) or containing An aryl group of 1 to 12 atoms (for example, an aryl group containing 1 to 12 carbon atoms (such as phenyl and naphthyl)). ^ R2 J η polymer (9) is characterized by the repeated units as shown in the following formula. The paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 Public Holiday ~ -14-(Please read the back first (Notes to fill out this page)

1231760 A7 ______B7 V. Polymers or copolymers of the invention ((Please read the notes on the back before filling out this page), or their copolymers. In the formula, n is an integer, and R1, R2, and R3 are unique or white. Nominal or amine groups having 1 to 20 carbon atoms (such as alkylamino groups having 1 to 5 carbon atoms in ethylamino groups) or aryl groups containing 1 to 12 atoms (for example, containing 1 to 12 carbon atoms) Atomic aryl groups (such as phenyl and naphthyl, etc.), χ_ are exchangeable negatively charged ion pairs, respectively.

X

Printed by the Consumer Cooperatives of the Intellectual Property Office of the Ministry of Economic Affairs. Among the above polymers, the negatively charged ion pairs can be organic ions, inorganic ions, or a combination of these. Suitable inorganic ions such as halides (especially chlorides), phosphates, phosphites, carbonates, thiocarbonates, sulfates, hydrogen sulfates, hydroxides, nitrates, persulfates Ions of sulfite and sulfide. Suitable organic ions, such as acetate, ascorbate, benzoate, citrate, dihydrocitrate, monohydrocitrate, oxalate, succinate, tartrate, taurocholic acid, glycine Each ion of aminocholate and cholate. In addition, the so-called super-absorbent polymer means that its lg can absorb more than 10niL of water and change into a non-flowable gel state. Even if a certain amount of pressure is applied, the absorbed water does not change. Will escape, showing high water retention polymer. Examples of the water-absorbing polymer include the polymers described above as examples of the hygroscopic polymer. The ingot containing 50% by weight of the hygroscopic polymer of the present invention can be applied to Chinese paper standard (CNS) A4 (210X297 mm) at this paper size. -15- 1231760 Printed by A7, Consumer Cooperative of Intellectual Property Bureau, Ministry of Economic Affairs B7 V. Description of the invention (12) Manufactured by conventional methods such as direct powder compression method or indirect powder compression method. In addition, when tableting, various additives usually used may contain suitable excipients, disintegrating agents, fluidizing agents, binding agents, slip agents, and the like, as long as they do not hinder the object of the present invention. Additives for colorants and fragrances. The content of the fluidizing agent is preferably 1% by weight or less relative to the total weight of the plain tablet. The content of the binder is preferably 20% by weight or less with respect to the total weight of the tablet. The content of the slip agent is preferably from 0.05 to 1% by weight relative to the total weight of the plain tablets. Examples of the excipient include cellulose or cellulose derivatives such as crystalline cellulose and low-substituted hydroxypropyl cellulose; corn starch or starch derivatives such as corn starch and dextrin; lactose, white sugar, and D-Sugar or sugar alcohol such as mannitol; inorganic excipients such as dried aluminum hydroxide gel, precipitated calcium carbonate, synthetic aluminum silicate, magnesium aluminosilicate, light anhydrous silicic acid, and calcium hydrogen phosphate . Examples of the binder include cellulose or cellulose such as hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, and carboxymethyl ethyl cellulose. Derivatives; starches such as maize starch or its alpha compounds; starch derivatives such as hydroxypropyl starch; pullulan, polyvinyl alcohol, polyvinylpyrrolidone, acacia rubber, gelatin, tragacanth, etc. Examples of the disintegrating agent include Carmellose or its sodium or calcium salt and cellulose derivatives such as Crosscarmellose; starch or starch derivatives such as wheat starch and sodium carboxymethyl starch; and sodium alginate. Examples of fluidization aids include hardened oil, polyethylene oxide (please read the precautions on the back before filling this page}

This paper size applies to China National Standard (CNS) A4 (210X 297 mm) -16- 1231760 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the invention (13) Chemical oil, polyethylene oxide Fatty acid esters of anhydrous sorbitol such as stearate, polyethylene oxide polypropylene glycol, polysorbate and sorbitan sesquioleate, glyceryl monostearate and Lauromacrogol, etc. Examples of slip agents include higher fatty acids such as stearic acid, magnesium stearate, and calcium stearate, and metal salts thereof; sodium lauryl sulfate, sucrose fatty acid esters, and colloidal silica. The plain tablet containing 50% by weight or more of a hygroscopic polymer according to the present invention can be manufactured by mixing the ingredients. The method for preparing a tablet used in the present invention is not particularly limited, and known methods such as a direct powder compression method, an indirect powder compression method, a dry particle compression method, and a wet particle compression method can be suitably used. The ingot of the present invention containing 50% by weight or more of a hygroscopic polymer has a moisture content of 10% by weight or less, and is suitable for preliminary heating without completely losing thermal expansion energy. The veggie ingot containing 50% or more hygroscopic polymer according to the present invention may be specifically according to the method described in Japanese Patent Application Laid-Open No. 10-330269 (International Publication No. W098 / 44933) or International Publication No. WO00 / 22008. Manufactured by the method described. The coating agent used for coating in the present invention is not particularly limited, and generally the coating agent used when coating with tablets is used. For example, a film coating agent is prepared by dissolving a thin film base agent with purified water as a solvent, dispersing a lubricating agent, a light-shielding agent, and a pigment, and mixing the solid content and ice to obtain the film coating agent. In addition, the coating agent used in the present invention may contain various additives such as a plasticizer, a smoothing agent, a light-shielding agent, and a pigment as a solid content. The above-mentioned solid content concentration is usually 1 to 20%. (Please read the precautions on the back before filling out this page) The size of the bound and bound paper is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) -17-! 231760 A7 B7 V. Description of the invention (y is used as above As the film base of the coating agent, general additives can be used, and in accordance with the purpose of the lozenge, a gastric soluble film coating base ^ or an enteric or slow release film coating base can be appropriately selected. As a gastric soluble film Coating bases, such as cellulose derivatives such as hydroxypropyl cellulose and hydroxypropyl methyl cellulose; polyvinyl acetal diethylamino acetate, aminoalkyl methacrylate copolymer-E [ EudragitE (commercial name), romfalmer company] and polyvinyl pyrrolidone and other synthetic polymers; dextrin, pullulan, zein, sodium alginate, gelatin and white sugar, etc .; 0 as enteric or release film coating base, For example, cellulose derivatives of ethyl cellulose, hydroxypropyl methyl cellulose phthalic acid, hydroxypropyl methyl cellulose acetate succinic acid, hydroxymethyl ethyl cellulose and cellulose fumarate acetate; Acrylic copolymer L or LD [EudragitL, L-30D55 (trade name), romfalmer company] and amino alkyl acrylate copolymer-RS [EudragitRS (trade name), romfalmei * company] and other acrylic polymers; natural materials such as shellac These can be used singly or in combination of two or more kinds. Among them, cellulose derivatives are preferred, and hydroxypropyl cellulose and hydroxypropyl methyl cellulose are particularly preferred. The use amount of the film base agent does not need to be special It may be 50% by weight or more based on the film layer. Examples of the plasticizer used in the coating agent include Macrogol (polyethylene glycol), triethyl citrate, triacetin, and medium. Chain fatty acid triglycerides, glycerin, etc. The amount of plasticizer added is relative to the total solids content in the coating solution, usually 50% by weight and less than 0. This paper's standard applies to China National Standard (CNS) A4 specifications (210X297 mm) ) (Please read the precautions on the back before filling out this page)-Packing · 11 Printed by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economics -18-1231760 A7 B7 V. Description of the invention (1 is now used as the coating agent Slippery Examples include talc, stearic acid, magnesium stearate, and sucrose fatty acid esters. The amount of the lubricating agent added is generally less than 50% by weight relative to the total solids content in the coating liquid. As used in Examples of the light-shielding agent or pigment of the coating agent include metal oxides such as titanium oxide, yellow ferric oxide, red ferric oxide, and black ferric oxide, and tar-based pigments. The amount of the light-shielding agent or pigment added It is usually 50% by weight or less with respect to the total solid content in the coating liquid. The coating method for the coating liquid used in the present invention is not particularly limited, and known methods can be appropriately used, but commercially available The coating device is preferably a spray-coated veggie tablet. The coating amount of the coating liquid is not particularly limited, but the film amount is preferably in an amount of 1 to 10% by weight based on the tablet. In addition, the above film is coated on the plain tablets, and after the surface roughness of the tablets is repaired at the initial stage of the coating, if sufficient strength can be obtained (film strength in the case of film coating agents), then the same or different coatings can be applied. The coating liquid is applied according to a conventional method. The coating in the manufacturing method of the present invention is the above-mentioned vegetarian tablet containing 50% or more hygroscopic polymer under the condition that the thermal expansion energy of the tablet is not completely lost (that is, at least The condition that the thermal expansion energy is still partially remained), preliminary heating is performed, and secondly, when the coating liquid is applied or after the application, it can be performed under the condition that the tablet is fully expanded. Here, thermal expansion refers to the deformation caused by the increase of the tablet thickness caused by heating. In addition, the above-mentioned conditions under which the thermal expansion energy of the plain tablets are not completely lost, and the conditions under which the tablets are sufficiently expanded are determined by measuring the increase in the thickness of the tablets (plain tablets) due to heating. The thickness of pastilles due to heating This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page) -Installation ·--tv Intellectual Property Office of the Ministry of Economic Affairs Printed by the Employee Consumption Cooperative -19-1231760 A7 B7 V. Description of the invention (Increase the amount to keep the tablets at a predetermined temperature (such as 30 ° c, 40 ° C, 50 ° C, 60 ° C, 70 ° C and 80 ° C, etc.), the thickness of the tablets is measured at regular intervals (for example, every 5 minutes, 10 minutes, etc.), and can be obtained by comparing the thickness of the tablets before heating. The conditions for the swelling of the tablets are as described above. The measured increase in the thickness of the tablets is close to the maximum condition, and the appropriate temperature must be set when coating the coating liquid or after coating, or about the two. Specifically, the thickness of the tablets when the tablets are held for a certain period of time under these conditions. The increase amount is a condition of 0.5% or more of the thickness of the plain tablets. The condition of 2.5% or more is preferable, and the condition of 5.0% or more is more preferable. When the tablets are sufficiently expanded, the temperature of the tablets is usually maintained. The thickness increase at this temperature for 20 minutes becomes The temperature of 0.5% or more of the thickness of the ingot is preferably a temperature at which the above-mentioned increase in thickness becomes 2.5% or more of the thickness of the ingot, and the temperature at which the above-mentioned increase in thickness becomes more than 5.0% of the thickness of the ingot is particularly preferable. The conditions for the tablet to swell sufficiently are to keep the tablet temperature above 40 ° C when the coating liquid is applied, and after the coating solution is applied, the tablet temperature is preferably maintained above 50 ° C. The hygroscopic polymer is In the case of polyallylamine polymers, the temperature of the tablets is such that the tablets are sufficiently expanded. When the coating solution is applied, the temperature of the tablets is maintained at 40 to 70 ° C. After the coating solution is applied, the temperature of the tablets is maintained at 55 to 85t is preferred. The retention time under the condition that the tablet is fully expanded is the time when the smoothness of the tablet surface has achieved the purpose. Usually it is more than 30 minutes, preferably more than 60 minutes, especially more than 90 minutes. As mentioned above, if this paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) (please read the precautions on the back before filling out this page) -20- Ministry of Economy Printed by the Consumer Goods Cooperative of the Citizenship and Welfare Bureau 1231760 A7 B7 _ V. Description of the invention (1) When the strength is sufficient (film strength in the case of film coating agent), then the same or different coating liquid can be applied in accordance with the usual method Therefore, the tablet can be used for more than enough time to satisfy the purpose of coating (for purposes other than improving the smoothness of the surface of the tablet, such as improving the stability of the main drug, improving the usability, and controlling the release time of the main drug). When the wet polymer is a polyallylamine polymer, the conditions for the tablets to expand sufficiently when the coating liquid is applied, usually the tablet temperature is 40 to 60 ° C, 60 to 400 minutes, and the tablet temperature is 40 to 60 ° C, preferably 120 to 400 minutes. In addition, when the hygroscopic polymer is a polyallylamine-based polymer, the conditions for swelling after the coating solution is applied to the tablets are usually 55 to 85 ° C for more than 10 minutes. The temperature is 55 to 85 ° C, preferably 30 minutes or more, and the tablet temperature is 60 to 80 ° C, more preferably 30 minutes or more. The so-called pre-heating without completely losing the thermal expansion of the plain tablets means the thickness of the tablets when the pre-heating of the tablets (the plain tablets) increases in thickness to keep the tablets fully expanded. When the preheating is performed under the condition of less than 3/5 of the increase amount, the increase in the thickness of the tablet after the preheating becomes 2/5 or less of the increase in the thickness of the tablet under the condition that the tablet is fully expanded. It is advisable to perform preliminary heating under the conditions, so that the increase in the thickness of the tablets after the preliminary heating becomes such that the increase in the thickness of the tablets under the condition that the tablets are sufficiently expanded is 1/5 or less of the increase in the thickness of the tablets It's better. When the hygroscopic polymer is a polyallylamine polymer, preliminary heating is performed without completely losing the thermal expansion energy of the plain tablets. The tablet temperature is in accordance with the Chinese national standard (CNS) A4 specification (210X297) at this paper standard. Li) (Please read the notes on the back before filling this page)

-21-1231760 Printed by A8 B7, 8 Industrial Consumer Cooperatives, Bureau of Intellectual Property, Ministry of Economic Affairs, V. 5. Description of the invention (1 $ is suitable for pre-heating of 40 to 60 ° C. Hygroscopic polymer is polyallylamine polymer At this time, the time required for pre-heating without completely losing the thermal expansion of Su-do is usually about 5 to 60 minutes, preferably 5 to 20 minutes. At this time, the pre-heating is performed at a temperature of 50 It is advisable to perform it at 70 ° C. In order not to completely lose the thermal expansion energy, the pre-heating of the plain tablets is performed in such a way that the moisture content of the plain tablets does not significantly change the shape or hardness of the tablets. The increase in the thickness of the agent varies depending on the holding temperature. For example, to maintain the tablet at 50 ° C for 10 minutes, the thickness increase is 10% for 10 minutes. When the hygroscopic polymer is a polyallylamine polymer, the moisture content of the plain tablets is based on the drying reduction method of 105 ° C-3 hours, and the moisture content is 3% by weight or more and 10% by weight. The following is preferable, and more preferably 3% by weight or more and 8% by weight or less. The method of moisture content is not particularly limited. The hygroscopic polymer and various additives of the raw materials are adjusted in advance to the required moisture content state and mixed, and the method of making tablets is the simplest. Others also produce vegetarian tablets. The method of keeping in the humidity-adjusted environment or the method of drying by a common drying method such as a vacuum drying method, but at this time, care must be taken not to heat the tablet to cause thermal expansion. The moisture content of the tablet can be measured by the drying reduction method, The measurement conditions are preferably 1051-3 hours. In addition, when storing plain tablets, in order to prevent moisture absorption, we must consider moisture-proof packaging, etc. 0 This paper size applies Chinese National Standard (CNS) A4 specifications (210 > < 297 mm) ) (Please read the notes on the back before filling this page)

-22- 1231760 A7 B7 V. Description of the invention (19) In addition, the temperature of the above tablets can be measured using various commercially available machines, for example, a non-contact thermometer can be used for measurement. The measurement error of the non-contact thermometer is generally the reading i: about 1% (or ± 2 ° C). (Please read the precautions on the back before filling out this page) The following examples and test examples will explain the present invention in more detail. The temperature of the tablet was measured using a portable non-contact thermometer PT-3LF (manufactured by OPTEX). [Example 1] 8.62% by weight of a polyallylamine / epichlorohydrin crosslinked polymer (general name: seberamer hydrochloride (r-INN), water content of 5.5% by weight), 13.62% by weight of crystalline fibers And 0.12% by weight of raburiwakkus 101 (hardened ramie oil) were put into a V-type mixer, mixed at 15 rpm for 15 minutes, then 0.05% by weight of magnesium stearate was added thereto, and then mixed at 15 rpm for 1 minute. This mixed powder was beaten with a rotary beater (X-45 type manufactured by Hiromi Iron Works) to produce a plain ingot (a moisture content of 5.5% by weight and a hardness of 10 kgf). The moisture content was measured by the dry weight loss method (105t :, 3 hours). Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs [Example 2] The plain tablets obtained in Example 1 were dried in a desiccator with silicone, and prepared into 3.0% by weight plain tablets and water. A content of 3.8% by weight. Moisture content was measured by dry weight loss method (10 5 ° C, 3 hours). -23- This paper size is in accordance with Chinese National Standard (CNS) 8-4 specification (210X 297mm) 1231760 A7 B7 V. Description of the invention (2 () [Example 3] The vegetarian tablet obtained in Example 1 was placed in a room for suction. Wet was prepared into a vegetarian tablet with a moisture content of 8.0% by weight. The moisture content was measured by the dry weight loss method (105 ° C '3 hours). [Test Example 1] The vegetarian tablet obtained in Example 1, Put in a constant temperature bath at 40 ° C, 50 ° C, 60 ° C and 70 ° C, and take samples every 5 minutes to 60 minutes, and measure the thickness of the lozenge by the thickness meter. It shows the change with time at various temperatures. One of the results of the increase in the thickness of the tablets (the difference from before the warming) is shown in Figure I. (Please read the precautions on the back before filling this page) [Experimental Example 2] The vegetarian tablets (the water content is 5.5% by weight) obtained in Example 1 and the vegetarian tablets (the water content is 3.0% by weight and the water content is 3.8% by weight) obtained in Example 2 And the plain tablets (water content of 8.0% by weight) obtained in Example 3 were placed in constant temperature baths of 60 ° C, 70 ° C and 80 ° C, Samples are taken every 10 minutes to 30 minutes, and the thickness of the tablets is measured in thickness. The results of the increase in the thickness of tablets at various temperatures over time are shown in Figures 2 to 5 respectively. Example 4] 6.5% by weight of hydroxypropyl methylcellulose, 1% by weight of Macrogol 6000, 2% by weight of titanium oxide and 0.5% by weight of talc were dissolved. The Chinese paper standard (CNS) A4 specifications (210X297 mm) -24- Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy 1231760 A7 __ B7 V. Description of the invention (20 or refined water dispersed in 90% by weight, prepared into a coating solution. Second, 5.0 kg of the plain tablets prepared in Example 1 were put into a coating machine (manufactured by POWREX, DRC-500). The air supply temperature was set at 55 ° C, and preliminary drying was performed for 10 minutes. The temperature of the tablets at the end of the preliminary drying was 51 ° C. Next, set the air supply temperature to 53 ° C. After spraying the spray liquid at 6mg / min to 60 minutes, spray at i2mg / min for 210 minutes. During this time, the tablet temperature was 45 to 49 ° C. After spraying, set the air temperature to 70 ° C and dry it afterwards 180 minutes. After the drying is completed, the temperature of the tablet is 73 ° C. [Example 5] The vegetarian tablet prepared in Example 1 and the coating solution prepared in Example 4 were used. 195.8 kg of Example 1 was used. The prepared tablet is put into a coating machine (FREUND, HCF-150). The air setting temperature is 70 ° C, and preliminary drying is performed for 9 minutes. The temperature of the tablet at the end of preliminary drying is 5 ° C. Next, The gas setting temperature is 58 to 80 ° C, the spray volume of the spray solution is 240 mL / min to 60 minutes, the spray is performed at 300 mL / min for 120 minutes, and then the spray is performed at 360 mL / min for 222 minutes. The tablet temperature during this time was 48 to 54 ° C. After spraying is completed, the air supply temperature is set to 70 ° C, and post-drying is performed for 3 60 minutes. After the post-drying is completed, the tablet temperature is 75 ° C. [Example 6] The same vegetarian tablet as in Example 1 and the coating solution prepared in Example 4 were used. 207.4 kg of the plain tablets prepared according to Example 1 were put into a coater (manufactured by Freund, AQC-150F). Air supply set temperature is 50 to This paper size is applicable to China National Standard (CNS) A4 specification (210X 297 mm) (Please read the precautions on the back before filling this page)

-25- 1231760 A 7 B7 5. Description of the invention (2 $ Roughness) The scanning laser microscope can be used for screen analysis or a commercially available machine such as a surface roughness measuring machine. [Table 1] Tablet surface smoothness Example 4 Good Example 5 Good Comparative Example 1 Defective (Please read the precautions on the back before filling out this page-packing · [Possibility for industrial use] As shown by the above test examples The manufacturing method of the present invention solves the problems of the prior art, and can provide coating lozenges with excellent surface smoothness, uniform coating, and a hygroscopic polymer as the main component, which have not been provided in the past. Under the condition that the thermal expansion energy of the plain ingot which contains more than 50% of hygroscopic polymer in the present invention is not completely lost (that is, at least the thermal expansion energy of the plain ingot still partially remains) For preliminary heating, secondly, when coating the coating solution or after coating, heat the tablet to thermally expand it and repair the rough surface of the tablet that occurred at the beginning of the coating. The manufacturing method is a new and unique method. It is a very useful and useful way to open up new insights. This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm). Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. -27-

Claims (1)

A8 B8 C8 D8 VI. Application for Patent Scope 1 91 1 36392 Chinese Patent Application Amendment (Please read the precautions on the back before filling this page) Amendment on January 27, 1994 A method for manufacturing a coated tablet having a wet polymer as a main component, which is characterized in that a plain tablet containing 50% by weight or more of a hygroscopic polymer is used under the condition that the thermal expansion energy of the plain tablet is not completely lost. Then, preliminary heating is performed, and secondly, when the coating liquid is applied or after coating, the surface shape of the tablet is repaired while keeping the tablet fully expanded. 2. The manufacturing method according to item 1 of the scope of patent application, wherein the coated tablet is a film-coated tablet. 3. The manufacturing method according to item 1 or item 2 of the scope of patent application, wherein the moisture content of the plain ingot is 10% by weight or less. 4. The manufacturing method according to item 1 or item 2 of the scope of patent application, wherein the hygroscopic polymer contained in the ingot is 70% by weight or more. 5. The manufacturing method according to item 1 or item 2 of the scope of patent application, wherein the hygroscopic polymer is a polyallylamine polymer. Printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 6. The manufacturing method according to item 5 of the patent application, wherein the hygroscopic polymer is a polymer obtained by cross-linking and polymerizing polyallylamine with epichlorohydrin. 7 _ — A coated tablet, characterized by being obtained by the manufacturing method according to any one of claims 1 to 6 of the scope of patent application. This paper size applies to China National Standard (CNS) A4 (210X297 mm)