TW200819144A - Composition with increased photo-stability - Google Patents

Abstract

Provided is an orally solidified composition with increased photo-stability capable of easily avoiding discoloration and decomposition of amlodipine or pharmaceutically allowable salts thereof due to light. The orally solidified composition with increased photo-stability contains amlodipine or a pharmaceutically allowable salt thereof and ferric oxide, and has no coating.

Description

200819144 IX. INSTRUCTIONS: 广广 [Technical field to which the invention belongs] / The present invention relates to an oral solid composition and preparation containing amlodipine, which enhances photostability. [Prior Art] Amlodipine (Am 1 odi pi ne) which belongs to the dihydrogen 11-bite dance antagonist, has anti-hypertensive treatment due to its sufficient and constant vasodilating action and difficulty in causing tachycardia. The method plays an important role. However, amlodipine is a compound which is not easily photodecomposed in the dihydroabiidine compound, but decomposes when the amount of exposure is large to lower its function as an activating substance. Therefore, the oral solid composition containing amlodipine requires a technique for ensuring the stability of light. In the past, for the formulation of drugs which are unstable, there are known methods for the stabilization of various kinds of music. For example, in the patent document, a soft capsule in which a coloring agent is dispersed in a film is disclosed, and nifedipine which is a drug which is unstable to light is enclosed, and the softness of nifedipine which is decomposed or deteriorated by light is prevented. capsule. Further, the patent document discloses a capsule preparation in which an activated vitamin (10) is formulated by a hard capsule containing: a dye or a red iron oxide. These techniques all contain a coloring agent in a capsule film which is coated with light and is unstable, and is difficult to apply to tablets, granules, fine granules, powders and the like. On the other hand, Patent Document 3 discloses that a tablet of a dihydropyridine derivative is coated with a film in which iron oxide is formulated to form a tablet which is stable to light. However, this technology increases the coating step, the time and labor required 318705 5 200819144 : Increases and increases production costs. In addition, it is necessary to divide and use (4), and it is easy to cause trouble because the coating line is masked, and the blade surface is exposed after the division, and the light stabilization effect cannot be expected. Furthermore, the above technique cannot be applied to a formulation which cannot be subjected to coating engineering for some reason. For example, an orally disintegrating preparation may damage its rapid disintegration and rapid solubility in the oral cavity when it is applied as a whole, and its function cannot be exhibited. In addition, although the rapid disintegration of the preparation can be maintained by coating only the raw material medicine in the preparation or the particles containing the raw material medicine, at this time, part of the coated preparation in the oral cavity does not disintegrate and dissolve, This point predicts that it is very difficult to take e-learning agents. X, Patent Document 4 discloses a light-stabilizing pyridine-based compound containing oxidized oxime as a light-shielding agent and containing edible yellow No. 5, ferric oxide, and yellow ferric oxide as colorants. However, the features disclosed in the literature are based on the solid dispersion of arididipine by a suitable excipient, and the coating liquid containing the coloring agent and the sunscreen is sprayed. The preparation of the covered product is disclosed (the second page of the patent document 4, the first block, the first row, the fifth row, the second row, the fourth row, the second page, the second, the third row, the third row, the third page, the fourth block, the fifth The example of the line). In the light stabilization method in which a coated tablet, granule, fine granule, or powder is not applied, Patent Document 5 discloses that one or more substances selected from the yellow and red coloring agents are formulated in a light-labile fat. A composition that enhances light stability by a soluble drug. Further, Patent Document 6 discloses an oral solid composition obtained by wet granulation in which a coloring agent is added to a powder containing a photolabile drug. Further, Non-Patent Document i discloses the addition of yellow 318705 6 200819144 two-color two, and in the case of nifedipine, it is possible to suppress the generation of oxides due to light and to suppress the decrease in the content of the main music. However, this document is related to the description of helmets and amlodipine. ..., Patent Document 1: Japanese Laid-Open Patent Publication No. 55-22645. Patent Document 2: Japanese Laid-Open Patent Publication No. Hei-4-46122. Patent Document 3: Japanese Laid-Open Patent Publication No. 2003-104888. Patent Document 4: Japanese Laid-Open Patent Publication No. 2003-104887. _ Patent Document 5: Japanese Laid-Open Patent Publication No. Hei 2-7-583. Patent Document 6: Japanese Laid-Open Patent Publication No. 2000-191516. Non-Patent Document 1: International Pharmaceutical Journal (Internati〇nal J〇urnai f Pharmaceutics), Issue 1, 3, 1994, pp. 69-76. SUMMARY OF THE INVENTION [Problems to be solved by the invention] The problem to be solved by the present invention is to provide a light stability which can be easily prevented from discoloration and decomposition by amlodipine or a pharmaceutically acceptable salt thereof due to light. • A modified oral solid composition. [Means for Solving the Problem] The hydrazine-based compound and t, due to the light stability of amlodipine, are not a problem in the range of use as a general pharmaceutical product. The inventors of the present invention found that amlodipine differs from the fact that it has a discoloration in the range where the content of light is not detected. 2 Prevention of such coloration is a research subject. In the above Non-Patent Document 1, the f color is completely undescribed. Naturally, there is no description or darkness about this subject. The subject of the 5 Hai literature is to improve the nifedipine lozenge in the light of 400 singer light 318705 7 200819144 (w-Candle) for 14 days, there will be 45% decomposition, on the other hand, as shown in the following test example, The amount of money produced by the agent is about 1%, and the degree of decomposition is completely different. = The main problem of amlodipine is to prevent coloration. It is known that it is completely different from the content reduction of the main subject of Shi Xiao. It has also been found by the inventors and the like that the coloring behavior itself is completely different from that of the sulfonate, that is, the actual silking agent is confirmed, and the nifedipine is prepared in the same manner. The tablets in the Ding and Ding Ding are placed in the tile first. The color is not changed. In the nifedipine opening, the color is in the color of the stone, and the original color is yellow. It fades in a few hours, and the color is slightly yellowish in the case of amlodipine in the case of amlodipine. It can be seen that the color reaction of the clamped color reaction and the color reaction of amlodipine are completely different. The method of whether the air quality of the first method can be applied to the 6th Λ Λ is obviously impossible. Ingredients, the raw materials of the literature 5 and a, the tolerant effective is tetramethine (menate calorie (6) and Sodecone (Sofalcone), not only does not check the heat of the '', the second hydrogen. :::Up=The effect of the same structure leveling. It is more difficult to predict the ammonia chloride_f progress from the above literature. The inventors of the present invention also found that the test example is as follows: the titanium oxide is formulated into t-amyldipine. Conversely, it will promote the use of stabilizers for the decomposition of light;;! Also, as an anti-oxidant, such as butylhydroxytoluene, butylhydroxy alum, 318705 8 200819144 ether, as an antioxidant, these antioxidants are It can suppress the production of decomposition products caused by ammonia chloride, but it is also found that at least on the ammonia level, the light caused by the light means the same behavior. Therefore, the iron oxide is mixed with ammonia to suppress the color change effect. The system is completely unpredictable. With the evolution of the aging society, due to various physiological functions, such as low cattle or dementia, the function of ingesting food (eg, (4) the age of the temple is reduced or the number of elderly people with disabilities is increasing. Such reading agents In the case of oral administration of drugs, it is difficult to take medication. In another busy modern society, it is not necessary to choose the time or place to use it. Water, + and low capacity and convenient to carry sigma preparation. The present inventors: 1. = obtained: the oral disintegration of amlodipine which improves the administration of the above @, which shows the function of the disintegration in the oral cavity There is no method for achieving the light stabilization of amlodipine in the preparation without treatment. Therefore, the inventors of the present invention (4) can be applied if a key agent for amlodipine which is not stable to light can be provided. Oral collapse in the mouth of the mouth, I Mingyan nine and so on, after careful investigation, found that the distribution of iron oxide in ammonia chloride or its pharmaceutically acceptable salt, you do not need to use light stabilization = coating, / ρ It is very easy to obtain a light-stabilized oral solid composition containing amlodipine. It has also been found that by applying this technique, iron oxide can be easily administered to amlodipine or a pharmaceutically acceptable salt thereof. Excellent π-cavity disintegration preparation The present invention has been completed by light stabilization. 318705 9 200819144 That is, the present invention relates to the following items: 乂[] § has (a) amlodipine or its pharmaceutically acceptable I and (b) The oral solid composition according to the above-mentioned item [1], wherein the titanium-containing composition is not contained in the above-mentioned item [1], and [3] is as described above. Oral solid composition as described in [1] or [2], orally disintegrating preparation. /, /, 瘫, [4] as described in any of the above items ]1] to [3] The oral solid composition comprising the following (3) to ((1) component: (a) amlodipine or a pharmaceutically acceptable salt thereof, (b) iron oxide, (c) mannitol, d) Corn house powder. [5] The oral solid composition according to any one of the above-mentioned items, wherein the composition further comprises sodium stearyl fumarate, and the oral solid composition comprises an oral cavity collapse. Unsinking. [6] The oral solid composition according to the above [5], wherein the (a) amlodipine or a salt thereof is contained in the oral solid composition, and is determined by amlodipine. 2 to 5% by weight, the content of the (b) iron oxide in the oral solid composition is 〇2% by weight, and the amount is 70 to 90% of the (c) mannitol in the oral solid composition % by weight, the content of the (d) corn starch in the oral solid composition is 5 to 318705 10 200819144 15 5 % by weight, and: (e) the fumaric acid stearin - in the oral solid composition The content is from 1 to 3% by weight. (1) The oral solid composition according to any one of the above [1] to [6] wherein the iron oxide is yellow iron oxide. [8] The oral solid composition according to any one of the above [1] to [7], which comprises (a) amlodipine or a pharmaceutically acceptable salt thereof, and (8) a mixture of iron oxide. [9] The oral solid composition according to any one of the above-mentioned items, wherein (a) amlodipine or a pharmaceutically acceptable salt thereof, and (b) oxidation A composition obtained by granulating a mixture of iron. [Effects of the Invention] According to the present invention, it is possible to provide a mouth-solid composition containing a light-stabilizing ammonia gas level very easily. In addition, it is possible to maintain the easy-to-use preparation such as the orally disintegrating tablet of amlodipine which cannot be applied, by the light stabilization, and to provide a patient who is difficult to swallow the body such as an 8-year-old person. Or a solid solid composition of amlodipine which is easy to take under any circumstances. [Embodiment], due to amlodipine, ie [2-(2-aminoethoxymethyl)_4_(2_chlorophenyl^4-hydro-6-methylpyridine-3, 5-dicarboxylic acid 3-ethyl 5-methyl ester; | has a photoactive center, so there are (s) _ (-) isomers and (E) - ( + ) isomers, which can be used in the present invention One or a mixture thereof, wherein the (s)-(-) isomer and the racemate are preferably used. 318705 11 200819144 A pharmaceutically acceptable salt of amlodipine, for example, with hydrochloric acid, chlorine, and acid , sulfuric acid, citric acid, acetic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, citric acid, gluconic acid, succinic acid, salicylic acid, tartaric acid, benzoic acid, toluene sulfonic acid, etc. The salt is composed of amlodipine Besylate which is formed with benzenesulfonic acid. The iron oxide of the present invention is produced, for example, yellow ferric oxide, iron oxide, and double emulsion-iron. , iron oxide red and iron oxide black, of which yellow diiron, iron oxide yellow, ferric oxide are preferred, and Puyi is better. /, Ba Yihuan one dosage form of the appropriate amount As the prepared iron oxide is too small in the case of a yellow iron oxide-containing spinner, sufficient effect cannot be obtained, so the heart:: is allocated to 10 coffee, and the better addition amount is for the competition. Li Qiao 01 to 5 wt%, f "' is preferably added in an amount of 0.05 to 5% by weight. The particle size of the iron oxide in the hair, as long as it can be uniformly dispersed, blended in the oral solid, to 0. 01 To, π f 〇.01 to be a good q in the present invention - Π Π, with 〇.1 to 0 · ^ m is better (_i) agent, dry two. Λ t such as 谬 Kang agent, gummy lozenge Formulations of granule preparations such as granules, fine granules, granules, etc., orally disintegrating preparations, etc., 318705 12 200819144: No need to use water when taking, no need to choose time The point of 'quick, soft candy, can be taken ° °.. is better, better for the mouth ^ ^ " clothing, oral disintegration preparation is the best. 'In particular, the intraoral disintegrating ingot is the S month layer refers to the most direct oral administration unit.) ^^PTP (press thro-h combined with two = 1::1° listed in the main drug, Excipients, disintegrating agents, one: dry type 4 or wet granulation, etc., if necessary, the resulting solid tape 彡* L, 仃 叙 溶液 啧 啧 啧 啧 啧The polymer, _ / , , sitting dry is equal to the outer side of the oral solid composition, the shape = the outer layer of the composition of the oral solid composition. In the upper ^ ^ solution, does not hinder the formation of general film Range =: Kind of additive. Coating refers to the formation of such coating layers. Other coating layers 'for example, capsules such as soft (four) or hard capsules. In the present invention, the content of amlodipine or a pharmaceutically acceptable salt thereof is not determined as follows: since the usual daily dosage is 2.5 to (4), the size of the coating agent is determined by amlodipine. It is preferred that amlodipine or a pharmaceutically acceptable salt thereof is added to the weight of 1 (). Among them, ',,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, It is preferably formulated to contain 1 to 6.2 wt%, more preferably 2 to 5 wt%. The orally disintegrating preparation in the present invention means rapid dissolution or disintegration without the need of water. It can be taken in the oral cavity, and it can also be taken in the same manner as the general preparation and water 318705 13 200819144. The dosage form is exemplified by powders, fine granules, granule preparations and lozenges. The time required for dissolution or disintegration in the oral cavity in the orally disintegrating granular preparation or the intraoral disintegration bond is usually within a minute, preferably within 45 seconds, more preferably within 3 seconds. ▲In the oral cavity disintegration preparation of the present affairs, from the point of view of taking Preferably, the water-soluble excipient is added by adding a water-soluble excipient, for example, a water-soluble sugar alcohol having a good sweet taste when taken, a saccharide, a sweet amino acid, and the like, wherein the water-soluble sugar Alcohol, saccharide, glycine and mixtures thereof are preferred, especially water-soluble sugar alcohols. The water-soluble sugar alcohol in the present invention means, for example, the addition of lg of sugar alcohol in water every 5 minutes. In seconds, when it is released within about 30 minutes, the amount of water required is less than 3Gml of sugar alcohol, etc. The water solubility:: such as: sorbitol, mannitol, maltitol, reduced starch sugar , xylose, isomalt (gianted palatinose, ?/latinit), erythritol, etc., or two or more thereof may be mixed at appropriate ratios. Among them, the preferred water-soluble sugar alcohol For example, mannitol, xylitol, erythritol, and mannitol, erythritol are more preferably mannitol. In the present invention, the water-soluble sugar alcohol is, for example, at 50 to 99.9 weights, of which 7 to 1; good, 7 to 9 weight% is better, especially 75 to 85 $ % is the best. Disintegration of plum, especially in terms of disintegration, 3 is better. The disintegrating agent is, for example, starch, carboxy τ-based fiber 318705 14 200819144 • Vitamin, Wei-based cellulose, It Methyl cellulose feeding, low substitution degree of propylene-based cellulose, It's methyl methacrylate powder, low substitution of ψ ψ 殿 殿 、, cross-linking '·竣 methyl cellulose nano (Cr〇Scarmellose s〇diun〇 , cross-linked poly-dimensional (Cr〇SP〇Vid〇ne), etc., these two or more can be mixed at a suitable ratio. Among them, the powder, the ruthenium-based cellulose, low substitution C Cellulose, sodium carboxymethyl starch, croscarmellose sodium, and crospovidone are preferred. It is more preferable to use starch, low-substituted hydroxypropylcellulose, sodium strontium, croscarmellose sodium, crosinized quinone, and hydroxypropylcellulose with low substitution degree. Especially good. The best is starch. The starch in the present invention means a starch which is derived from all natural starches which can be used for pharmaceuticals. For example, potato starch, corn starch, wheat starch, rice starch or soluble starch, partially gelatinized starch, gelatinized starch = propylated starch, etc., among which corn starch is preferred. The powdericidal content is, for example, preferably from 1 to 50% by weight, more preferably from 2 to 3% by weight, more preferably from 3 to 20% by weight, most preferably from 5 to 15% by weight. . In the orally disintegrating preparation of the present invention, the binding agent to be used is not particularly limited, and examples thereof include, for example, a topical powder (including a topical powder), a (tetra)-based cellulose, a L-propyl mercapto cellulose, a polyvinyl anthracene ketone, Gelatin, methyl fiber, gum arabic powder, polyvinyl alcohol, alkyl and ethyl cellulose. In the case of disintegration, it is said that it is not ideal for things other than money powder. The term "beauty" means that as long as it does not affect the orally disintegrating preparation, the protection is in a range that does not affect the dissolution or disintegration rate in the oral cavity, and the use amount of the light of the present invention: Other binders can be tolerated. In the oral solid composition of the present invention, in addition to the above ingredients, it is possible to use 318705 15 200819144: a non-toxic and inert additive generally used in the field. These mouths... 丨 丨 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝 贝For example, lactose, corn house powder, mannitol: sorbitol, erythritol, glycine, talc, kaolin = sulphur called butterfly, crystal fiber fiber II: calcium stearate: fumarate Lubricating agent such as sodium ester; carboxy thiol-based private field... skillful low degree of substitution (tetra)-based cellulose, dimethoprim sodium, cross-linking = sodium cellulose and other disintegrants; propyl cellulose, propyl Methyl cellulose, polyethylene ketone, gelatin, methyl cellulose, gum arabic powder, polyethylene glycol, alkyl acetate and other bonding agents; other colors: Bu, flavor, spices , adsorbents, preservatives, stabilizers, wetting agents, antistatic agents, pH adjusters, etc. ~ A lubricant is used in the manufacture of the tablet of the present invention, wherein magnesium stearate and sodium stearyl fumarate are suitable. In addition, 'acesulfame K can be added with acesulfame K: high-sweet artificial sweeteners such as saccharin, sodium saccharin, stevia, and sucra ose, or mint and spearmint , menthol, lemon, orange, grapefruit, pineapple, fruit, yoghurt and other scenting agents and spices. Especially when blended with aspartame and mint flavors, you can get a better feeling. The method for producing the oral solid composition of the present invention can be carried out by a known method such as granulation method, extrusion granulation method, crush granulation method, dry compact granulation method, fluidized bed granulation method, rotary granulation method, rotation The flow layer granulation method and the granulation method are used for the granulation method; for example, the wet tableting method, the direct tableting method, and the like. 16 318705 200819144 The following examples and comparative examples are described in more detail, but the invention is not limited thereto. Example 1 Lozenge Formulation (mg) [Table 1]

*1 Product name: D-mannitol (product of Kyowa Fermentation Co., Ltd.) *2 Product name: Corn Starch (XX16) W (product of Japan Food Chemical Co., Ltd.) ^ Commodity* : PRUV (Pe Sung St Pharmaceuticals Co., Ltd. (USA) Products ) Product Name··Yellow Ferric Oxide (Products of 癸 化 成 成 成 成 318705 200819144 ※5 Product Name·Ethylene Oxide (Products of 癸化化成公司) 6 Product Name: Refined arsenic oxide (Sakdo 勉Chemical company (Germany) ※ Product name: 3-tert-butyl-4-hydroxyanisole (product of Nacalai tesque company) *8 Trade name: 2,6-di-tert-butyl-pair age (Nacalai Tesque company product) ※9 product name: food person yellow No. 5 (sanrong source F· F· I· company product) Lu ※10 product name · edible yellow No. 5 | Lu Seiya (San Fung Yuen FFI company products) Name: Edible Red No. 5 (Sanyungwon FF·I·Company Products) ※12 Product Name·Edible Red No.1 (Sanyeon FFI·Company Products) Examples 1 to 3 and Comparative Examples 1 to 8 are in accordance with The formula shown in Table 1 is divided into 12 parts of the composition and mixed with chyle. After the combination, the amount of the formula is taken using a hydraulic press (manufactured by Riken Co., Ltd.) to obtain a key of 7 mm directly controlled by a pressure of 50 kgf. The test examples are as shown in Examples 1 to 3 and compared. The photosensitivity test was carried out for the preparations of Examples 1 to 8. The results of the appearance and oxide yield of the fluorescent lamp 4 iux (iux) for 2 weeks are shown in Table 2. Further, the oxide (2) -[(2-Aminoethoxy)methyl]-4-(o-chlorophenyl)- 6-mercapto-3, 5-tonidinedicarboxylic acid 3-ethylacetate 5-decyl ester) Analysis by liquid chromatography. H_PLC analysis 竺^ tube column · octadecyl-bonded tannin (average particle size is 5 // m, inner diameter 18 318705 200819144 is 4. 6mm, length is 15〇mm) (trade name is (3)

Nacalai tesque company) A liquid: 3〇mm〇i/L acid salt buffer (Qiu 6 〇) / sterol mixture (1:1) β solution: methanol / 30mmol B solution · 80% - 〇% Ladder detector: UV light. Detection wavelength: 237 nm. [Table 2 ]

Phosphate buffer (ρΗ6· 〇) mixture (19: 1) degrees. 1/2 (the amount of oxide is the area percentage value of HPLC multiplied by the value of the correction factor of 2 (due to the ultraviolet absorption of the oxide is due to the ammonia chloride)). 318705 19 200819144 • It can be seen from Table 2 that the preparation of Comparative Example 1 which was not completely photo-stabilized, the yield of the 'outer (four) large' oxide was also more than 1%. On the other hand, in comparison with the preparation containing titanium oxide of Example 2, not only the discoloration was not suppressed, but the amount of oxide generation was also increased. The method of applying the coating layer to achieve light stabilization is generally applied by using titanium oxide having a strong light-shielding effect, and it is found that the titanium oxide is directly mixed with the main drug and the excipient, and the ammonia is produced instead of the coating. The stability of the light of the ground will deteriorate. Therefore, it is generally understood that the idea of light stabilization can be obtained by mixing a substance having a strong coating power with a main drug or an excipient, and the like cannot be applied to an ammonia gas level. Further, Comparative Examples 3 and 4 were prepared by adding a butyl group as an antioxidant and a preparation of butyl group-based toluene, and a comparative example 6 was added to a preparation of a 5-color No. 5 aluminum lake. The yield of the object ί cannot suppress the appearance change. Therefore, it can be seen that the addition of an antioxidant or a pigment:: is effective. </ br> White, respectively, Comparative Examples 5, 7 and 8 of the preparations of the edible yellow No. 5, the edible yellow No. 3 and the edible red (10) other yellow and red pigments of the 唬 Temple were not able to suppress the appearance change and the oxide yield. Therefore, it can be seen that there is generally no light stabilization effect. I, from the above, it is known that the generation of the sunscreen, the antioxidant, the dye inhibiting oxide, and/or the appearance change, and the preparation of the yellow iron oxide or the ferric oxide are relatively high. 1 Inhibit its appearance change and oxide production. Therefore, the use of the general side:, two inhibition of appearance changes and oxide yield, with amlodipine and oxidized 4 inch 疋 combination can inhibit the appearance of changes and oxide production. , '. 318705 20 200819144 [Industrial Feasibility]: According to the present invention, it is possible to easily prevent amlodipine or its pharmaceutically acceptable salt from providing light stability by discoloration and decomposition caused by light. The oral solid composition. Thereby, the quality of the orally disintegrating preparation of amlodipine or a pharmaceutically acceptable salt thereof can be improved, and at the same time, a simple and portable packaging form can be made feasible, so that an elderly person or a busy modern society can conveniently Carrying, without taking in water, can easily take amlodipine or its pharmaceutically acceptable salts at any site. 21 318705

Claims (1)

200819144 X. Patent Application Range: 1. An oral solid composition characterized by (a) amlodipine or a pharmaceutically acceptable salt thereof, and (b) iron oxide, and having no coating layer. 2. The oral solid composition of claim 1, wherein the titanium oxide is substantially not contained. 3. The oral solid composition of claim 1 or 2 of the patent application, which is an orally disintegrating preparation. 4. The oral solid composition according to any one of claims 1 to 3, wherein the following (&amp;) to (1) component: (a) amlodipine (Ami) 〇 ciipine) or a pharmaceutically acceptable salt thereof, (b) iron oxide ' (c) mannitol, (d) corn starch. 5. s oral injection according to any one of claims 1 to 4. The solid composition 'wherein, further contains sodium stearyl fumarate, and the oral solid composition is an orally disintegrating ingot. 6. The oral solid composition of claim 5, wherein &quot; A (a) amlodipine or its salt in the oral solid form, and the summer content of the product, based on amlodipine (Amlodipine), 2 to 5% by weight, the (b) iron oxide The content in the oral solid composition is 至·〇3 to 2% by weight, and the content of the (c) mannitol in the oral solid composition is 22 318705 200819144 &quot; 70 to 90% by weight, π ' The (d) corn starch is present in the b-solid composition in an amount of 5 to 15% by weight, and &amp; ', (e) the sodium stearyl stearate The oral solid content of the oral solid composition is 1 to 3% by weight. The oral solid composition according to any one of the preceding claims, wherein the iron oxide is yellow trioxide 8. The oral solid composition according to any one of claims 1 to 7 wherein (a) Amiodi pine or a pharmaceutically acceptable salt thereof, and (b) A mixture of iron oxides according to any one of claims 1 to 8, which comprises (a) amlodipine or its medical music. A composition obtained by granulating a mixture of a salt of Shanggu Xu and a mixture of (b) iron oxide. 318705 23 200819144 VII. Designated representative map: None (1) The representative representative of the case is: () A brief description of the symbol of the representative figure: 8. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: The chemical formula that is not represented in this case. 4 318705