JP2012041290A - Solid preparation containing lafutidine - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a lafutidine-contained solid preparation wherein lafutidine is stabilized because its decomposition by light and heat is effectively prevented.SOLUTION: Provided are a lafutidine-contained preparation characterized by containing lafutidine, and Food Yellow No. 5, Food Red No. 102, or a mixture of these colorants, and a manufacturing method thereof ; a method for restraining the generation of analogous materials of lafutidine characterized by coating the lafutidine-contained solid with a covering agent containing Food Yellow No. 5, Food Red No. 102, or a mixture of these colorants ; and a method for photostabilizing and thermal stabilizing the lafutidine.

Description

  The present invention relates to a lafutidine-containing solid preparation useful for the treatment of patients such as gastric ulcer, duodenal ulcer and anastomotic ulcer.

Lafutidine has H ₂ receptor antagonism and is used to treat gastric ulcer, duodenal ulcer, anastomotic ulcer, reflux esophagitis, gastric mucosal lesion in acute gastritis, gastric mucosal lesion in acute exacerbation of chronic gastritis, etc. Has been.

  However, lafutidine has a problem that it decomposes by light or heat. When an active ingredient of a pharmaceutical is decomposed, it is necessary to suppress degradation as much as possible because there is a possibility that the efficacy of the medicine is lowered and safety is impaired.

  Examples of the preparations that suppress degradation of the pharmaceutical preparation by light include, for example, soft capsules for containing photolabile compounds in which edible yellow No. 5 is uniformly dispersed in a soft capsule film to prevent photodegradation of nifedipine as much as possible. (Refer to Patent Document 1), powder containing a light-unstable drug such as sofalcone, nifedipine, vitamin Ds, vitamin Ks, etc., edible yellow No. 4, No. 5, edible red No. 3, No. 102, A light-stabilized oral solid composition (see Patent Document 2) formed by wet granulation with a binding liquid containing a colorant such as yellow ferric oxide, ferric oxide, iron oxide such as amlodipine and yellow ferric oxide Oral solid compositions with improved light stability (see Patent Document 3) and the like are known. However, these preparations have no description or suggestion about the photostabilization of lafutidine.

On the other hand, a soft capsule obtained by encapsulating an oily solution of active vitamin D ₃ in a soft capsule skin containing a white pigment and yellow iron oxide and / or red iron oxide is known. Describes that the active vitamin D ₃ is excellent in light stability and heat stability (see Patent Document 4). However, although this soft capsule can improve the light stability of the active vitamin D ₃ class, it does not improve the thermal stability. That is, as shown in Tables 1 and 5 of Patent Document 4, Comparative Example 1 in which no white pigment (titanium oxide), yellow iron oxide and red iron oxide are added to the soft capsule skin is the most 1α-hydroxyvitamin. D ₃ of high thermal stability, both were added one of these thermal stability of examples 1-5 and Comparative example 2 is also decreased, white pigments, yellow iron oxide and red iron oxide thermal stability It is clear that it has not contributed to the improvement of sex. Therefore, patent document 4 cannot be said to suppress the decomposition | disassembly by the heat | fever of a pharmaceutical formulation. Of course, Patent Document 4 has no description or suggestion about the light stabilization and heat stabilization of lafutidine.

Japanese Patent Laid-Open No. 55-22645 JP 2000-191516 A JP 2006-306754 A WO01 / 015702 Publication

  An object of the present invention is to provide a stabilized lafutidine-containing solid preparation in which the degradation of lafutidine in the lafutidine preparation by light or heat is effectively suppressed.

  As a result of diligent research to achieve the above-mentioned object, the present inventor has obtained a lafutidine-containing solid preparation containing lafutidine and a colorant that is edible yellow No. 5 and / or edible red No. 102, and in particular, a plain tablet containing lafutidine. It has been found that according to a lafutidine-containing solid preparation in which a solid such as elementary granules is coated with a coating agent containing the colorant, both the light stability and the heat stability are excellent. The present inventor has made further studies based on such knowledge, and has completed the present invention.

  The present invention provides the following lafutidine-containing solid preparation and method for producing the same, a method for suppressing the formation of a related substance of lafutidine, and a method for stabilizing and heat-stabilizing lafutidine.

  1. 1. A lafutidine-containing solid preparation comprising lafutidine and a coloring agent which is edible yellow No. 5, edible red No. 102 or a mixture thereof.

  2. Item 1. The lafutidine-containing solid preparation according to item 1, wherein the solid substance containing lafutidine is coated with a coating agent containing a coloring agent which is edible yellow No. 5, edible red No. 102 or a mixture thereof.

  3. Item 3. The lafutidine-containing solid preparation according to Item 2, wherein the solid substance containing lafutidine is in the form of an uncoated tablet or elementary granule.

  4). A method for producing a lafutidine-containing solid preparation, comprising coating a solid containing lafutidine with a coating containing a coloring agent which is Food Yellow No. 5, Edible Red No. 102 or a mixture thereof.

  5. A method for inhibiting the production of a related substance of lafutidine, which comprises coating a solid containing lafutidine with a coating containing a coloring agent which is edible yellow No. 5, edible red No. 102 or a mixture thereof.

  6). A method for stabilizing and heat-stabilizing lafutidine, comprising coating a solid containing lafutidine with a coating containing a colorant which is edible yellow No. 5, edible red No. 102 or a mixture thereof.

  According to the lafutidine-containing solid preparation of the present invention, it contains lafutidine and a colorant that is edible yellow No. 5 and / or edible red No. 102, in particular, solids such as uncoated tablets and elementary granules containing lafutidine. By coating with a coating agent containing the above colorant, the following remarkable effects can be obtained.

  (1) Since the decomposition by light and the decomposition by heat of lafutidine in the lafutidine-containing solid preparation is effectively suppressed over a long period of time, a stabilized lafutidine-containing solid preparation is provided. Also provided are a method for inhibiting the formation of a luffidine related substance, and a method for stabilizing and heat stabilizing lafutidine.

  (2) Since the above-mentioned lafutidine-containing solid preparation is suppressed from decomposition by light and heat, it has few impurities such as luffidine-related substances and prevents deterioration of the medicinal effect and safety over a long period of time. it can.

  (3) Also, according to the method for producing a lafutidine-containing solid preparation of the present invention, a solid containing lafutidine is coated with a coating containing a colorant which is edible yellow No. 5 and / or edible red No. 102. Thus, a light-stabilized and heat-stabilized lafutidine-containing solid preparation can be easily prepared.

FIG. 1 is a graph showing the results of a photostability test of lafutidine-containing tablets obtained in Example 1, Example 2 and Comparative Examples 1 to 4. FIG. 2 is a graph showing the results of the thermal stability test of the lafutidine-containing tablets obtained in Example 1, Example 2 and Comparative Examples 1 to 4.

Lafutidine-containing solid preparation The lafutidine-containing solid preparation of the present invention contains lafutidine and a coloring agent that is food yellow No. 5 and / or food red No. 102, and is usually used in the pharmaceutical field. Even if it is a solid preparation such as tablets, granules, pills, capsules, etc. containing various pharmacologically acceptable additives used, such as excipients, disintegrants, binders, etc. Alternatively, it may be a lafutidine-containing coated solid preparation obtained by coating a solid material such as uncoated tablets and elementary granules containing lafutidine with a coating agent containing the colorant.

Solids containing lafutidine The solids include, preferably, uncoated tablets and elementary granules composed of lafutidine and additives such as excipients, disintegrants and binders.

Lafutidine is a medicinal ingredient of the solid preparation of the present invention, and its chemical name is (±) -2- (furfurylsulfinyl) -N- [4- [4- (piperidinomethyl) -2-pyridyl] oxy- (Z) -2-butenyl] acetamide. As mentioned above, lafutidine has an H ₂ receptor antagonistic action and is useful as a therapeutic agent for gastric ulcers and the like.

The additive lafutidine is usually used in combination with at least one pharmacologically acceptable additive of excipients, disintegrants and binders.

  Examples of the excipient include starches such as crystalline cellulose and corn starch; lactose, powdered sugar, granulated sugar, glucose, mannitol, light anhydrous silicic acid, talc, magnesium oxide, magnesium carbonate, calcium carbonate and the like. These excipients can be used alone or in combination of two or more.

  Examples of the disintegrant include carmellose calcium, carmellose sodium, croscarmellose sodium, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, and starches. These disintegrants can be used alone or in combination of two or more.

  As binders, conventional binders such as sucrose, gelatin, gum arabic powder, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose (carmellose), crystalline cellulose / sodium carboxymethylcellulose, polyvinylpyrrolidone, pullulan, dextrin Tragacanth, sodium alginate, pregelatinized starch and the like. These binders can be used alone or in combination of two or more.

  The ratio of the additive which is at least one of these excipients, disintegrants and binders can be selected from the range of about 200 to 3000 parts by weight with respect to 100 parts by weight of lafutidine, and usually 300 to 2500 parts by weight. The amount is preferably about 500 to 2000 parts by weight.

  In addition to pharmacologically acceptable additives such as excipients, disintegrants, and binders, lafutidine further includes other pharmacologically acceptable conventional additives such as lubricants, Fluidizers, antistatic agents, surfactants, flavoring agents, wetting agents, fillers, extenders, adsorbents, preservatives (such as preservatives), buffers, disintegration extenders, colorants, etc. may be added. Good.

  Examples of the lubricant include magnesium stearate, light anhydrous silicic acid, talc, stearic acid, calcium stearate and the like. Examples of the antistatic agent include light anhydrous silicic acid. Examples of surfactants include anionic surfactants such as sodium alkyl sulfate; nonionic surfactants such as polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid esters, and polyoxyethylene castor oil derivatives. Can do. Examples of the corrigent include sweeteners such as sucrose, lactose, mannitol, xylitol, saccharin, sodium saccharin, aspartame, stevioside; and flavorings. Examples of the wetting agent include polyethylene glycol (macrogol), glycerin, propylene glycol and the like.

  These other conventional additives can be used alone or in combination of two or more. These components are not particularly limited in content in the final formulation.

  In the present invention, solids such as uncoated tablets and elementary granules containing lafutidine can be produced according to methods known in the pharmaceutical field. For example, lafutidine and additives such as excipients, disintegrants, binders, etc. are mixed, granulated, dried, sized, mixed with disintegrants / lubricants, tablets, using commonly used solvents A plain tablet can be manufactured by performing each operation of these according to a method well-known in the said field | area. Moreover, an elementary granule can be manufactured by operations up to the sizing operation among these operations. Among these operations, the granulation operation may be performed using an apparatus such as a stirring granulator, a fluidized bed granulator, a Brabender, or a twin screw granulator. Moreover, tableting can be performed using a commercially available tableting machine.

Coatings containing a coloring agent which is Food Yellow No. 5 and / or Edible Red No. 102 As coating agents containing a coloring agent which is Food Yellow No. 5 and / or Edible Red No. 102 used in the present invention, various forms are available. In general, in application, the colorant may be coated with a coating agent known in the art such as hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, sucrose as necessary. What is blended can be used in the form of an aqueous solution, aqueous dispersion, organic solvent solution or organic solvent dispersion. Here, the content of the colorant which is Food Yellow No. 5 and / or Food Red No. 102 in the coating is usually preferably about 0.02 to 2.0% by weight, and preferably 0.06 to 1. More preferably, it is about 5% by weight.

  In the present invention, it is essential to use a specific colorant that is Food Yellow No. 5 and / or Food Red No. 102 as a coating agent. By such a specific colorant, the light stability of raftidine as a medicinal component and Thermal stability can be remarkably improved. The chemical name of this edible yellow No. 5 is 2-hydroxy-6-sulfonate naphthalene-1-azo- (4′-benzenesulfonic acid) disodium, and the chemical name of edible red No. 102 is 2-hydroxyazonaphthalene -4 ', 6,8-trisulfonic acid trisodium salt.

  When coating the above coating on uncoated tablets, elementary granules, etc., it is preferably carried out by means such as a film coating machine, a fluidized bed granulator or the like.

  The coating amount of the coating agent is 3 to 12 weights with respect to 100 parts by weight of solids such as uncoated tablets and elementary granules containing lafutidine as a coloring agent which is Food Yellow No. 5, Edible Red No. 102 or a mixture thereof. About 5 parts by weight is preferable, and about 5 to 10 parts by weight is more preferable.

  In coating the uncoated tablets, uncoated granules, etc., the uncoated tablets, uncoated granules, etc. may be pre-coated on the uncoated tablets, uncoated granules, etc. . For the precoating and overcoating, for example, a coating agent known in the art such as hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, sucrose, etc. can be used.

  The lafutidine-containing solid preparation of the present invention can be used in various usage forms (for example, tablets, granules, pills, capsules, dry syrups, etc.), but is preferably used in the form of tablets.

  When using the lafutidine-containing solid preparation of the present invention, humans are effective in treating gastric ulcers, duodenal ulcers, anastomotic ulcers, reflux esophagitis, gastric mucosal lesions of acute gastritis, gastric mucosal lesions in acute exacerbation of chronic gastritis, etc. An amount may be administered. The dose may vary depending on the patient's age, weight, symptoms, sex, etc., but is usually divided into 1 or several doses per day, and is orally administered, for example, in the range of 5 to 160 mg converted to lafutidine. be able to.

  In the solid preparation of the present invention, for example, the total amount of related substances after storage for 4 weeks at 60 ° C. is less than 0.4% by weight. Here, as the related substance, 2- (furfurylsulfonyl) -N- [4- [4- (piperidinomethyl) -2-pyridyl] oxy- (Z) -2-butenyl] acetamide and the like can be mentioned.

  The solid preparation of the present invention may be packaged in PTP (press-through package) or bottle (eg, plastic bottle, glass bottle, aluminum can). Further, a deodorant, a desiccant, an oxygen scavenger, etc. may be enclosed during packaging.

  The present invention is characterized in that a solid substance containing lafutidine is coated with a coating agent containing a coloring agent which is edible yellow No. 5, edible red No. 102 or a mixture thereof. Provide a method for suppressing The coating agent, the coating method, and the like containing a colorant that is lafutidine, edible yellow No. 5, edible red No. 102, or a mixture thereof are as described above.

  Further, the present invention is characterized in that the solid matter containing lafutidine is coated with a coating containing a coloring agent which is food yellow No. 5, food red No. 102 or a mixture thereof, Also provided is a method of stabilization and thermal stabilization. The coating agent, the coating method, and the like containing a colorant that is lafutidine, edible yellow No. 5, edible red No. 102, or a mixture thereof are as described above.

  EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated further more concretely, this invention is not restrict | limited at all by these Examples.

Example 1
(1) Preparation of uncoated tablets 420 g of lafutidine and 1541.4 g of lactose hydrate were mixed and pulverized with a hammer mill (trade name “Atomizer”, manufactured by Fuji Powder Co., Ltd.) to obtain a mixed pulverized powder. The obtained mixed pulverized powder 1868 g, crystalline cellulose 720 g, corn starch 80 g, croscarmellose sodium 160 g were put into a fluidized bed granulator (trade name “FLO-5B”, manufactured by Freund Corporation), and hydroxypropylcellulose (product) The fluidized bed was granulated by spraying 2080 g of 5.0 wt% aqueous solution of “HPC-L” (manufactured by Nippon Soda Co., Ltd.). The obtained granulated powder was sized using a sizing machine (trade name “Power Mill”, manufactured by Dalton Co.) to obtain a sized powder. 800 g of the obtained sized powder, 241.2 g of lactose hydrate, 87.3 g of crystalline cellulose, 69.9 g of corn starch, 52.4 g of croscarmellose sodium, 28.4 g of hydroxypropylcellulose, 8.7 g of light anhydrous silicic acid , 21.8 g of magnesium stearate was mixed with a mixer (trade name “VM-5”, manufactured by Fuji Paudal Co., Ltd.), and the resulting mixed powder was mixed with a rotary tableting machine (trade name “VIRGO-”). 512 ”(manufactured by Kikusui Seisakusho Co., Ltd.) and using a mortar with a diameter of 5.5 mm and an R facet with a radius of curvature of 7 mm to make a tablet weight of 60.0 mg and a thickness of 2.45 mm. An uncoated tablet was obtained.

(2) Uncoated tablet coating 100 g of the uncoated tablet obtained in (1) above, 20 g of hydroxypropylmethylcellulose (trade name “AW-4”, manufactured by Samsung Chemical Co., Ltd.), 2 g of Macrogol (PEG6000), 3 g of talc, Using a coating solution obtained by dissolving and suspending 0.3 g of edible yellow No. 5 in 175 g of purified water, the coating machine (trade name “HC-LABO”, manufactured by Freund Corporation) is 8.3% with respect to the uncoated tablet weight. (W / w) Coating was performed to obtain film-coated tablets.

Example 2
100 g of the uncoated tablet obtained in (1) of Example 1, 20 g of hydroxypropyl methylcellulose (trade name “AW-4”, manufactured by Samsung Chemical Co., Ltd.), 2 g of Macrogol (PEG6000), 3 g of talc, edible red No. 102 Using a coating solution obtained by dissolving and suspending 0.3 g in 175 g of purified water, the coating machine (trade name “HC-LABO”, manufactured by Freund Corporation) uses 8.3% (w / w) based on the weight of the uncoated tablet. ) Coated to obtain film-coated tablets.

Comparative Example 1
To 100 g of the plain tablet obtained in (1) of Example 1, 20 g of hydroxypropylmethylcellulose (trade name “AW-4”, manufactured by Samsung Chemical Co., Ltd.), 2 g of Macrogol (PEG6000), and 3 g of talc are added to 175 g of purified water. Using the dissolved and suspended coating solution, the coating machine (trade name “HC-LABO”, manufactured by Freund Corporation) was used to coat 8.3% (w / w) based on the weight of the uncoated tablet. Obtained.

Comparative Example 2
To 100 g of the uncoated tablet obtained in (1) of Example 1, 17 g of hydroxypropylmethylcellulose (trade name “AW-4”, manufactured by Samsung Chemical Co., Ltd.), 2 g of Macrogol (PEG6000), 3 g of talc, 3 g of titanium oxide Using a coating solution dissolved and suspended in 175 g of purified water, a coating machine (trade name “HC-LABO”, manufactured by Freund Corporation) was used to coat 8.3% (w / w) with respect to the uncoated tablet weight. Film-coated tablets were obtained.

Comparative Example 3
To 100 g of the uncoated tablet obtained in (1) of Example 1, 20 g of hydroxypropylmethylcellulose (trade name “AW-4”, manufactured by Samsung Chemical Co., Ltd.), 2 g of Macrogol (PEG6000), 3 g of talc, yellow iron sesquioxide Using a coating solution obtained by dissolving and suspending 0.3 g in 175 g of purified water, the coating machine (trade name “HC-LABO”, manufactured by Freund Corporation) uses 8.3% (w / w) based on the weight of the uncoated tablet. ) Coated to obtain film-coated tablets.

Comparative Example 4
To 100 g of the uncoated tablet obtained in (1) of Example 1, 20 g of hydroxypropylmethylcellulose (trade name “AW-4”, manufactured by Samsung Chemical Co., Ltd.), 2 g of Macrogol (PEG6000), 3 g of talc, and iron sesquioxide 0 Using a coating solution in which 3 g was dissolved and suspended in 175 g of purified water, it was 8.3% (w / w) based on the weight of the uncoated tablet using a coating machine (trade name “HC-LABO”, manufactured by Freund Corporation). Coating was performed to obtain film-coated tablets.

  Table 1 shows the formulation of the coating component per uncoated tablet (60.0 mg). In the table, HPMC represents hydroxypropylmethylcellulose.

  Next, the photostability test and the thermal stability test of the lafutidine-containing coated tablets obtained in Example 1, Example 2 and Comparative Examples 1 to 4 were performed. The photostability test was carried out under white fluorescent lamp irradiation (2000 Lux) for 14 days, 28 days, and 42 days, stored under unwrapped condition. In addition, the thermal stability test was carried out under storage conditions of 60 ° C. and stored for 14 days and 28 days in an unwrapped open state.

  For the coated tablets at the start and after each stability test, the peak area of lafutidine and the peak area of each related substance were examined using HPLC, and the sum of the ratios of the peak areas of each related substance to the peak area of lafutidine, Calculated. The HPLC measurement method is as follows.

HPLC measurement method Detector: UV absorption photometer (measurement wavelength: 220 nm)
Column: “Octadecylsilylated silica gel” (particle size 5 μm, column inner diameter 3 mm, column length 250 mm, manufactured by GL Sciences Inc.)
Column temperature: Constant temperature around 40 ° C. Mobile phase A: Dissolve 1.36 g of potassium dihydrogen phosphate in 900 ml of water, add 1 ml of triethylamine, and further add water to 1000 ml, and use phosphoric acid to adjust the pH to 5.0 Adjust to.
Mobile phase B: Acetonitrile Mobile phase feeding: Mixing ratio of mobile phases A and B is 0/5 minutes after sample injection, A / B is 85/15, and 5/25 minutes is 85 / 15-70 / A concentration gradient of 30 is set, a concentration gradient of 70/30 to 20/80 is set for 25 to 45 minutes, a concentration gradient of 20/80 to 85/15 is set for 45 to 47 minutes, and 85/15 is set after 47 minutes.
Flow rate: Adjust so that the retention time of lafutidine is about 20 minutes.
Area measurement range: 60 minutes.

  Table 2 shows the results of starting the light stability test and conducting the light stability test for 14 days, 28 days and 42 days for the lafutidine-containing tablets obtained in Example 1, Example 2 and Comparative Examples 1 to 4. The total relative substance peak ratio (%) to the peak area of lafutidine was shown.

  Moreover, the graph of the photostability test result about the lafutidine containing tablet obtained in Example 1, Example 2, and Comparative Examples 1-4 shown in Table 2 in FIG. 1 was shown.

  From Table 2 and FIG. 1, by covering the uncoated tablets containing lafutidine with a coating containing a coloring agent which is edible yellow No. 5 or edible red No. 102, the generation of related substances under light irradiation is suppressed. It is clear that the light stability is remarkably improved. On the other hand, when the colorant which is iron sesquioxide (Comparative Example 4) is used, although the light stability improvement of the same level as that of the present invention is observed, titanium oxide (Comparative Example 2) and yellow ferric oxide (Comparative). It is clear that no significant improvement in light stability is observed when using the colorant of Example 3).

  Table 3 shows the results of lafutidine when the heat stability test was started and the heat stability test was conducted for 14 days and 28 days for the lafutidine-containing tablets obtained in Example 1, Example 2 and Comparative Examples 1-4. The total related substance peak ratio (%) with respect to the peak area is shown.

  Moreover, the graph of the result of the thermal stability test about the lafutidine containing tablet obtained in Example 1, Example 2, and Comparative Examples 1-4 shown in Table 3 in FIG. 2 was shown.

  From Table 3 and FIG. 2, by covering the uncoated tablets containing lafutidine with a coating containing a coloring agent which is food yellow No. 5 or food red No. 102, the generation of related substances under high temperature conditions is suppressed. It is clear that the thermal stability is remarkably improved. On the other hand, it is also clear that there is almost no improvement in thermal stability even when using colorants other than Food Yellow No. 5 and Food Red No. 102, such as titanium oxide, yellow iron sesquioxide and iron sesquioxide.

The solid preparation containing lafutidine of the present invention is useful for the treatment of gastric ulcer, duodenal ulcer, anastomotic ulcer, reflux esophagitis, gastric mucosal lesion of acute gastritis, gastric mucosal lesion in acute exacerbation of chronic gastritis, etc. It is effectively used in the pharmaceutical field.

Claims (6)

  1. A lafutidine-containing solid preparation comprising lafutidine and a coloring agent which is edible yellow No. 5, edible red No. 102 or a mixture thereof.   2. The lafutidine-containing solid preparation according to claim 1, wherein the solid containing lafutidine is coated with a coating containing a coloring agent which is edible yellow No. 5, edible red No. 102 or a mixture thereof.   3. The lafutidine-containing solid preparation according to claim 2, wherein the solid substance containing lafutidine is in the form of an uncoated tablet or elementary granule.   A method for producing a lafutidine-containing solid preparation, comprising coating a solid containing lafutidine with a coating containing a coloring agent which is Food Yellow No. 5, Edible Red No. 102 or a mixture thereof.   A method for inhibiting the production of a related substance of lafutidine, which comprises coating a solid containing lafutidine with a coating containing a coloring agent which is edible yellow No. 5, edible red No. 102 or a mixture thereof. A method for stabilizing and heat-stabilizing lafutidine, comprising coating a solid containing lafutidine with a coating containing a colorant which is edible yellow No. 5, edible red No. 102 or a mixture thereof.

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