WO2022065361A1 - Procédé de fabrication de substances granulaires - Google Patents

Procédé de fabrication de substances granulaires Download PDF

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Publication number
WO2022065361A1
WO2022065361A1 PCT/JP2021/034789 JP2021034789W WO2022065361A1 WO 2022065361 A1 WO2022065361 A1 WO 2022065361A1 JP 2021034789 W JP2021034789 W JP 2021034789W WO 2022065361 A1 WO2022065361 A1 WO 2022065361A1
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Prior art keywords
tramadol
granulated product
particle size
weight
granulated
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PCT/JP2021/034789
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English (en)
Japanese (ja)
Inventor
紳嗣 小黒
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日本臓器製薬株式会社
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Priority to JP2022552031A priority Critical patent/JPWO2022065361A1/ja
Publication of WO2022065361A1 publication Critical patent/WO2022065361A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids

Definitions

  • the present invention relates to a method for producing a granulated product containing tramadol or a pharmaceutically acceptable salt thereof (hereinafter, these may be collectively referred to as "tramadol") as an active ingredient. More specifically, the present invention relates to a method for producing a granulated product in which segregation of tramadol content is suppressed.
  • tramadol a pharmaceutically acceptable salt thereof
  • Tramadol (chemical names: (1RS, 2RS) -2-[(dimethylamino) methyl] -1- (3-methoxyphenyl) cyclohexanol) is a powerful narcotic analgesic for the indication of cancerous pain, etc. It is a non-narcotic analgesic (weak opioid) positioned between a strong opioid) and a non-steroidal anti-inflammatory drug (NSAID) for which mild pain such as headache and joint pain is indicated.
  • NSAID non-steroidal anti-inflammatory drug
  • Tramadol has a lower frequency of side effects on the respiratory, circulatory and digestive system than strong opioids such as morphine, and has medical usefulness as a drug that is less likely to cause tolerance, physical dependence, abuse, etc., and is currently in 100 countries around the world.
  • Various dosage forms of tramadol hydrochloride are sold in the above countries.
  • oral preparations such as tablets and capsules, including combinations, are very widely used as dosage forms that are
  • Examples of the method for producing an oral tramadol include a method of mixing tramadol with additives such as an excipient, a binder, and a disintegrant to produce a granulated product.
  • Granulation methods include dry granulation, which does not use water and maintains a dry state, and wet granulation, which uses a granulation solution containing water, a binder, etc. at the time of granulation. However, wet granulation is generally performed because it is easy to manufacture. Tablets can be produced by further adding additives to the obtained granulated product as necessary and compression molding (tableting), and other granulation products such as capsules can be produced using the granulated product. Dosage forms can be manufactured.
  • the produced granulated product has a problem that the tramadol content varies depending on the particle size, that is, segregation occurs. Further, for example, when tableting using the granulated product to produce a tablet, if the mortar of the tableting machine is filled with granulated products having uneven particle diameters and uneven particle diameters. , The tramadol content in the manufactured tablets will be different.
  • the granulated product when the granulated product is formulated into a capsule, if the capsule is filled with a granulated product having an uneven particle size, the tramadol in the manufactured capsule is filled. The content will be different. The segregation of tramadol content between these individual formulations causes problems in the uniformity of the formulations. Therefore, in order to produce a uniform pharmaceutical product, it is required that the granulated products produced in the manufacturing process have a uniform content of tramadol contained in each granulated product even if the particle size is different. ..
  • Patent Document 1 discloses a sustained release pharmaceutical composition in which tramadol finely powdered so as to have a predetermined particle size range and a hydrophilic polymer (hydroxypropylmethylcellulose) are dry-mixed and directly compressed. More specifically, in this document, by setting tramadol in a predetermined particle size range, the amount of the inert ingredient in the pharmaceutical composition can be minimized and the desired sustained release property of tramadol is maintained. It states that it can be done. However, in this document, it is not possible to suppress segregation of tramadol content in the produced granules by using tramadol having a predetermined particle size distribution as in the present invention (details will be described later). No description or suggestion is given.
  • An object of the present invention is to provide a method for producing a granulated product containing tramadol, in which segregation of the tramadol content is suppressed between the granulated products and the granulated product has high uniformity.
  • tramadol used as a drug substance. That is, when the particle size distribution is measured by a laser diffraction method, tramadol having a predetermined particle size distribution (specifically, 8 to 50 ⁇ m as described later) (hereinafter, may be referred to as “this tramadol”) is used.
  • main granules the segregation of the tramadol content in the produced granules (hereinafter sometimes referred to as "main granules") can be suppressed. Based on this finding, the present inventors have completed the present invention by conducting further studies.
  • the present invention includes, for example, the following aspects. However, the present invention is not limited to these, and those that achieve the same object by substantially the same means are included in the present invention.
  • Use of its pharmaceutically acceptable salt Use of its pharmaceutically acceptable salt.
  • (21) It has a particle size distribution in which d50 is 8 to 50 ⁇ m when the particle size distribution is measured by a laser diffraction method when producing a granulated product containing tramadol or a pharmaceutically acceptable salt thereof as an active ingredient.
  • (22) The production method according to (21) above, wherein the particle size distribution of tramadol or a pharmaceutically acceptable salt thereof is d50 of 10 to 45 ⁇ m.
  • (23) The production method according to (21) or (22) above, wherein the particle size distribution of tramadol or a pharmaceutically acceptable salt thereof is 45 to 220 ⁇ m in d90.
  • a method for producing a granulated product containing tramadol or a pharmaceutically acceptable salt thereof according to the present invention as an active ingredient (hereinafter, may be referred to as "the present production method") is used when producing the granulated product.
  • the particle size distribution is measured by a laser diffraction method, tramadol having a particle size distribution in which d50 is 8 to 50 ⁇ m or a pharmaceutically acceptable salt thereof (this tramadol) is used. Since the granulated product (main granulated product) produced by this production method suppresses segregation of the active ingredient contained therein and has high uniformity, the present production method and this granulated product are extremely difficult. It is highly useful.
  • the particle size distribution is measured by a laser diffraction method, and the tramadol having a predetermined particle size distribution or a pharmacy thereof.
  • the present invention relates to a manufacturing method using a locally acceptable salt.
  • the particle size distribution of tramadol or a pharmaceutically acceptable salt thereof that can be used as the active ingredient of the present granules varies depending on the drug substance manufacturer and the production lot, but d50 is usually 8 to 8 to. It is 50 ⁇ m, preferably 10 to 45 ⁇ m, and more preferably 10 to 40 ⁇ m.
  • the technical problem of the present invention can be solved only by defining the more general d50 as the standard of the particle size distribution of the present tramadol, but further by defining d90 as well. It is possible and preferable to limit the particle size of tramadol having a large crystal size.
  • d90 is specified, it is usually 45 to 220 ⁇ m, preferably 50 to 210 ⁇ m, and more preferably 55 to 200 ⁇ m.
  • the particle size distribution in this tramadol can be measured by a conventional method, but more specifically, a laser diffraction method (measuring device: Mastersizer 2000 [Malburn, distributed compressed air pressure: 2 to 4 Bar], SALD-3100). It can be obtained by volume distribution evaluation using [Shimadzu Corporation], etc.). From the obtained measurement results, when the total volume is 100%, the particle diameter when the cumulative volume is 50% from the smallest particle is called d50, and the particle diameter when the cumulative volume is 90% is called d50. It is called d90.
  • the "laser diffraction method” is also called a "laser diffraction scattering method”.
  • the method for preparing the particle size of this tramadol is not particularly limited, but it can be crushed to a predetermined particle size using a general crusher such as a pin mill, a hammer mill, or a jet mill.
  • the screen diameter of the crusher is not particularly limited, but it is preferable to use one having a screen diameter of 2 mm or more. Further, the particle size of this tramadol may be adjusted by sieving.
  • the granulated product is generally granulated by mixing the tramadol having a prepared particle size with an excipient, a disintegrant, a binder, etc. that can be usually used as a pharmaceutical additive. It can be manufactured according to the granulation method.
  • Granulation methods include dry granulation methods (dry roller compactor method, roll granulator method, etc.) and wet granulation methods (spray granulation method, stirring granulation method, extrusion granulation method, fluidized layer granulation method, etc.).
  • the present granulated product is not particularly limited, but is preferably produced by a wet granulation method, and more preferably, a fluidized layer granulation method is used.
  • this granulated product can be formulated into various dosage forms such as tablets, orally disintegrating tablets, effervescent tablets, capsules, granules, and dry syrups by further adding additives and tableting, if necessary. It can be formulated into a pharmaceutical formulation of.
  • the tramadol contained in this granulated product may be a pharmaceutically acceptable salt thereof.
  • any pharmaceutically acceptable acid addition salt can be used without particular limitation, and for example, hydrochloride, sulfate, nitrate, phosphate, fluorinated acid salt, and the like.
  • Inorganic acid salts such as hydrobromide, acetate, tartrate, lactate, citrate, fumarate, maleate, succinate, methanesulfonate, benzenesulfonate, toluenesulfonic acid. Examples thereof include organic acid salts such as salts, naphthalene sulfonates and camphor sulfonates.
  • tramadol hydrochloride which is the active ingredient of tramadol preparations that are commercially available as analgesics and are widely used clinically. Further, the stereoisomers, hydrates and solvates of tramadol are also included in tramadol which can be an active ingredient of the present granulated product.
  • the blending ratio of tramadol or a pharmaceutically acceptable salt thereof is not particularly limited and can be appropriately selected.
  • tramadol hydrochloride it can be 5 to 85% by weight, preferably 10 to 80% by weight, and more preferably 12 to 78% by weight with respect to 100% by weight of the present granulated product.
  • additives usually used as pharmaceutical additives can be used as long as the effects of the present invention are not hindered.
  • additives include, for example, excipients, disintegrants, binders, sustained release bases, plasticizers, solubilizers, surfactants, fluidizers, PH adjusters, wetting agents, antioxidants. , Preservatives, effervescent agents, sweeteners, flavoring agents, fragrances, colorants and the like. These should be appropriately selected and blended according to the type and characteristics of the pharmaceutical product to be manufactured, such as an orally disintegrating preparation, an immediate release preparation, a sustained release preparation, a dry syrup preparation, etc. Can be done.
  • the excipient that can be used as an additive for this granule is not particularly limited, but is lactose (hydrate), sucrose, D-mannitol, crystalline cellulose, powdered cellulose, corn starch, potato starch. , Partially pregelatinized starch, dextrin, pullulan, hydroxypropyl starch, macrogol and the like. These excipients may be used alone or in any combination of two or more. Preferred examples include, for example, the use of lactose hydrate and / or crystalline cellulose in the production of immediate release granules having immediate effect.
  • the blending ratio in the present granulation is not particularly limited, but for example, in the immediate release granulation, the present granulation is used. It can be 0 to 45% by weight, preferably 0 to 40% by weight, and more preferably 0 to 35% by weight with respect to 100% by weight of the product.
  • the blending ratio in the granulated product is not particularly limited, but for example, in the immediate release granulated product, 100% by weight of the granulated product is used. On the other hand, it can be 1 to 30% by weight, preferably 2 to 28% by weight, and more preferably 3 to 25% by weight. Further, for example, in a sustained release granulated product having a long-lasting medicinal effect, the above-mentioned additive can be not used.
  • the binder that can be used as an additive for the granules is not particularly limited, but is limited to methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose (hypromellose), and sodium carboxymethyl cellulose (sodium carmellose).
  • Etc. carboxyvinyl polymer, polyvinyl alcohol, polyvinylpyrrolidone (povidone), vinylpyrrolidone copolymer (copolyvidone), acrylic acid polymer, dextrin, gelatin, agar, xanthan gum, arabic rubber, purulan, tragant, alginic acid.
  • binders may be used alone, or two or more of them may be used in any combination.
  • preferred binders include, for example, the use of hydroxypropyl cellulose in the production of immediate release granules, hydroxypropyl cellulose and / or carboxyvinyl polymers in the production of sustained release granules, etc. Can be mentioned.
  • the blending ratio in the present granulated product is not particularly limited, but for example, in the immediate release granulated product, the present granulated product 100 It can be 0.1 to 3% by weight, preferably 0.3 to 2.5% by weight, and more preferably 0.5 to 2% by weight with respect to% by weight. Further, for example, in the sustained release granulated product, the content may be 35 to 90% by weight, preferably 38 to 88% by weight, and more preferably 40 to 85% by weight with respect to 100% by weight of the present granulated product. can.
  • the blending ratio in the granulated product is not particularly limited, but for example, in the sustained release granulation product, the blending ratio is 100% by weight of the granulated product. On the other hand, it can be 0.1 to 10% by weight, preferably 0.3 to 8% by weight, more preferably 0.5 to 5% by weight, and may not be used for immediate release granulation. It is possible.
  • the disintegrant that can be used as an additive for the granules is not particularly limited, but is limited to corn starch, sodium starch glycolate, crospovidone, carboxystarch sodium, carboxymethyl starch sodium, starch, and partially pregelatinized.
  • examples thereof include starch, lactose, calcium citrate, light anhydrous silicic acid, synthetic aluminum silicate crystalline cellulose, low-substituted hydroxypropyl cellulose, croscarmellose, croscarmellose sodium, carboxymethyl cellulose calcium, carmellose, hydroxypropyl starch and the like.
  • These disintegrants may be used alone or in any combination of two or more.
  • Preferred examples include, for example, the use of partially pregelatinized starch in the production of immediate release granules.
  • the blending ratio in the main granulation is not particularly limited, but for example, in the production of immediate release granulation, the main production It can be 10 to 45% by weight, preferably 13 to 40% by weight, more preferably 15 to 38% by weight with respect to 100% by weight of the granules, and is not used in the production of sustained-release granules. It is possible.
  • the colorant that can be used as an additive for the granules is not particularly limited, but is limited to titanium oxide, iron yellow oxide, iron black oxide, iron sesquioxide, yellow iron sesquioxide, zinc oxide, and brown oxidation. Examples include iron and tar pigments. These colorants may be used alone or in combination of two or more. Preferably, for example, yellow iron sesquioxide and / or iron sesquioxide and the like can be mentioned.
  • the blending ratio in the granulated product is not particularly limited, but is 0.01 to 100% by weight of the granulated product. It can be 0.5% by weight, preferably 0.03 to 0.4% by weight, and more preferably 0.05 to 0.3% by weight.
  • the blending ratio in the granulated product is not particularly limited, but is 0.005 to 0.1 with respect to 100% by weight of the granulated product. It can be% by weight, preferably 0.008 to 0.08% by weight, more preferably 0.01 to 0.05% by weight.
  • Example 1 Tramadol hydrochloride (d50: 59 ⁇ m, d90: 260 ⁇ m) was placed in an impact type crusher having a screen diameter of 2 mm and pulverized. 350 g of ground tramadol hydrochloride (d50: 17 ⁇ m, d90: 85 ⁇ m), 420 g of partially pregelatinized starch, 182 g of crystalline cellulose and 426 g of lactose hydrate were placed in a fluidized bed granulator and mixed well.
  • Example 2 Tramadol hydrochloride (d50: 59 ⁇ m, d90: 260 ⁇ m) was placed in an impact type crusher having a screen diameter of 2 mm and pulverized. 650 g of ground tramadol hydrochloride (d50: 17 ⁇ m, d90: 85 ⁇ m), 1928 g of hydroxypropyl cellulose and 26 g of carmellose sodium were placed in a fluidized bed granulator and mixed well. Here, 520.8 g of purified water was sprayed as a granulation liquid to granulate, and the mixture was dried. The obtained dried granulated product was placed in a granulator and sized to obtain a granulated product C. Further, as a comparative example, uncrushed tramadol hydrochloride was used in the same manner to obtain a granulated product D.
  • Example 3 Tramadol hydrochloride (d50: 136 ⁇ m, d90: 465 ⁇ m) was placed in an impact type crusher having a screen diameter of 2 mm and pulverized. 175 g of ground tramadol hydrochloride (d50: 25 ⁇ m, d90: 87 ⁇ m), 420 g of partially pregelatinized starch, 234 g of crystalline cellulose and 351 g of lactose hydrate were placed in a fluidized bed granulator and mixed well. Separately, 12 g of hydroxypropyl cellulose was dissolved in 330.9 g of purified water, and the entire amount of the granulation liquid prepared was sprayed to granulate and dry. The obtained dried granulated product was placed in a granulator and sized to obtain a granulated product.
  • Example 4 Tramadol hydrochloride (d50: 136 ⁇ m, d90: 465 ⁇ m) was placed in an impact type crusher having a screen diameter of 2 mm and pulverized. 325 g of ground tramadol hydrochloride (d50: 25 ⁇ m, d90: 87 ⁇ m), 1565 g of hydroxypropyl cellulose and 20 g of carmellose sodium were placed in a fluidized bed granulator and mixed well. Here, as a granulation liquid, 382 g of purified water was sprayed in its entirety, granulated, and dried. The obtained dried granulated product was placed in a granulator and sized to obtain a granulated product.
  • Example 5 Tramadol hydrochloride (d50: 141 ⁇ m, d90: 453 ⁇ m) was placed in an impact crusher having a screen diameter of 2 mm and pulverized. 700 g of ground tramadol hydrochloride (d50: 21 ⁇ m, d90: 60 ⁇ m), 420 g of partially pregelatinized starch, 78 g of crystalline cellulose and 180 g of lactose hydrate were placed in a fluidized bed granulator and mixed well.
  • Example 6 Tramadol hydrochloride (d50: 141 ⁇ m, d90: 453 ⁇ m) was placed in an impact crusher having a screen diameter of 2 mm and pulverized. 1300 g of ground tramadol hydrochloride (d50: 21 ⁇ m, d90: 60 ⁇ m), 1894 g of hydroxypropyl cellulose and 102 g of carmellose sodium were placed in a fluidized bed granulator and mixed well. Here, as a granulation liquid, 659.2 g of purified water was sprayed in its entirety, granulated, and dried. The obtained dried granulated product was placed in a granulator and sized to obtain a granulated product.
  • Example 7 Tramadol hydrochloride (d50: 213 ⁇ m, d90: 503 ⁇ m) was placed in an impact crusher having a screen diameter of 2 mm and pulverized. 1050 g of ground tramadol hydrochloride (d50: 28 ⁇ m, d90: 85 ⁇ m), 260 g of partially pregelatinized starch, and 68 g of crystalline cellulose were placed in a fluidized bed granulator and mixed well.
  • Example 8 Tramadol hydrochloride (d50: 186 ⁇ m, d90: 513 ⁇ m) was placed in an impact crusher having a screen diameter of 2 mm and pulverized. 1950 g of ground tramadol hydrochloride (d50: 23 ⁇ m, d90: 101 ⁇ m), 1750 g of hydroxypropyl cellulose and 120 g of carmellose sodium were placed in a fluidized bed granulator and mixed well. Here, as a granulation liquid, 764 g of purified water was sprayed in its entirety, granulated, and dried. The obtained dried granulated product was placed in a granulator and sized to obtain a granulated product.
  • Example 9 Tramadol hydrochloride (d50: 55 ⁇ m, d90: 297 ⁇ m) was placed in an impact crusher having a screen diameter of 2 mm and pulverized. 525 g of ground tramadol hydrochloride (d50: 21 ⁇ m, d90: 74 ⁇ m), 630 g of partially pregelatinized starch, 273 g of crystalline cellulose and 639 g of lactose hydrate were placed in a fluidized bed granulator and mixed well.
  • Example 10 Tramadol hydrochloride (d50: 55 ⁇ m, d90: 297 ⁇ m) was placed in an impact crusher having a screen diameter of 2 mm and pulverized. 975 g of ground tramadol hydrochloride (d50: 21 ⁇ m, d90: 74 ⁇ m), 2892 g of hydroxypropyl cellulose and 39 g of carmellose sodium were placed in a fluidized bed granulator and mixed well. Here, as a granulation liquid, 781.2 g of purified water was sprayed in its entirety, granulated, and dried. The obtained dried granulated product was placed in a granulator and sized to obtain a granulated product F.
  • Example 11 Tramadol hydrochloride (d50: 55 ⁇ m, d90: 297 ⁇ m) was placed in an impact crusher having a screen diameter of 10 mm and pulverized. 525 g of ground tramadol hydrochloride (d50: 39 ⁇ m, d90: 187 ⁇ m), 630 g of partially pregelatinized starch, 273 g of crystalline cellulose and 639 g of lactose hydrate were placed in a fluidized bed granulator and mixed well.
  • Example 12 Tramadol hydrochloride (d50: 55 ⁇ m, d90: 297 ⁇ m) was placed in an impact crusher having a screen diameter of 10 mm and pulverized. 975 g of ground tramadol hydrochloride (d50: 39 ⁇ m, d90: 187 ⁇ m), 2892 g of hydroxypropyl cellulose and 39 g of carmellose sodium were placed in a fluidized bed granulator and mixed well. Here, as a granulation liquid, 781.2 g of purified water was sprayed in its entirety, granulated, and dried. The obtained dried granulated product was placed in a granulator and sized to obtain a granulated product H.
  • the content of tramadol hydrochloride in the granulation on each sieve was measured by high performance liquid chromatography (internal standard method, isocratic conditions), and the ratio to the content of tramadol hydrochloride in the entire granulation ( Content by particle size:%) is calculated and shown.
  • the standard deviation was calculated from the average value of the tramadol hydrochloride content by particle size as an index of segregation of the active ingredient content between the granulated products. Examples of the results are shown in Tables 1 and 2.
  • the granulated products A and C using tramadol hydrochloride having a predetermined particle size distribution by grinding are compared with the granulated products B and D using unground tramadol hydrochloride, respectively. Since the content of tramadol hydrochloride for each particle size was close to 100% and the standard deviation value was small, it was confirmed that there was little variation and high uniformity. Further, as is clear from Table 2, in the granulated products E to H using the crushed tramadol hydrochloride, the content of tramadol hydrochloride according to each particle size is also close to 100%, and the standard deviation value is also obtained. It was confirmed that there was little variation and high uniformity because of the small size.
  • Examples 3 to 8 similarly, by using tramadol hydrochloride having a predetermined particle size distribution by pulverization, granulated products having high uniformity of tramadol hydrochloride content were obtained. From this result, it was shown that it is important that the tramadol hydrochloride used as a drug substance has a predetermined particle size distribution in order to produce a granulated product having a uniform tramadol hydrochloride content.
  • this production method it is possible to produce highly uniform granulated products in which segregation of tramadol content is suppressed.
  • the granulated product produced by this production method is used and formulated into various dosage forms, the tramadol content does not vary much and a highly uniform formulation can be obtained, so this production method is very useful. It is highly sexual.

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Abstract

L'invention a notamment pour objet de fournir un procédé destiné à fabriquer des substances granulaires d'une uniformité élevée en restreignant la ségrégation de la teneur en principe actif entre les substances granulaires, dans le cadre de la fabrication d'une préparation pharmaceutique comprenant un tramadol ou un sel pharmacologiquement acceptable de celui-ci en tant que principe actif.　Plus précisément, l'invention concerne notamment un procédé destiné à fabriquer des substances granulaires d'une uniformité élevée, selon lequel la ségrégation de la teneur en tramadol ou sel pharmacologiquement acceptable de celui-ci est restreinte par mise en œuvre d'un tramadol ou d'un sel pharmacologiquement acceptable de celui-ci, lequel tramadol présente une distribution granulométrique telle que ｄ５０ est compris entre ８ et ５０μｍ, lorsque la distribution granulométrique est mesurée par un procédé de diffraction laser.
PCT/JP2021/034789 2020-09-25 2021-09-22 Procédé de fabrication de substances granulaires WO2022065361A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007114376A1 (fr) * 2006-03-30 2007-10-11 Nippon Zoki Pharmaceutical Co., Ltd. Preparation pharmaceutique solide
JP2017210478A (ja) * 2016-05-23 2017-11-30 大原薬品工業株式会社 薬物高含有圧縮錠剤の安定な製造方法
WO2019130701A1 (fr) * 2017-12-26 2019-07-04 旭化成株式会社 Poudre de cellulose

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007114376A1 (fr) * 2006-03-30 2007-10-11 Nippon Zoki Pharmaceutical Co., Ltd. Preparation pharmaceutique solide
JP2017210478A (ja) * 2016-05-23 2017-11-30 大原薬品工業株式会社 薬物高含有圧縮錠剤の安定な製造方法
WO2019130701A1 (fr) * 2017-12-26 2019-07-04 旭化成株式会社 Poudre de cellulose

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