WO2017188361A1 - Comprimé contenant de la tosufloxacine tosilate - Google Patents

Comprimé contenant de la tosufloxacine tosilate Download PDF

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Publication number
WO2017188361A1
WO2017188361A1 PCT/JP2017/016681 JP2017016681W WO2017188361A1 WO 2017188361 A1 WO2017188361 A1 WO 2017188361A1 JP 2017016681 W JP2017016681 W JP 2017016681W WO 2017188361 A1 WO2017188361 A1 WO 2017188361A1
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Prior art keywords
tablet
powder
sieve
opening
granulated
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PCT/JP2017/016681
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English (en)
Japanese (ja)
Inventor
一美 田谷
侑輝 粕谷
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富山化学工業株式会社
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Priority to JP2018514690A priority Critical patent/JP6647395B2/ja
Publication of WO2017188361A1 publication Critical patent/WO2017188361A1/fr

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    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein

Definitions

  • the present invention relates to a tablet containing tosufloxacin tosylate which exhibits rapid dissolution and does not cause tableting troubles and is excellent in manufacturability.
  • Tosfloxacin is a new quinolone antibacterial agent having a broad antibacterial spectrum against Gram positive bacteria, Gram negative bacteria and anaerobic bacteria (Patent Document 1).
  • Patent Document 1 As a prescription and production method of a solid preparation containing tosufloxacin, it is known to prepare a preparation by mixing tosufloxacin tosylate hydrate, an organic acid having 2 to 6 carbon atoms and a general medical carrier ( Patent Document 2).
  • Patent Document 3 Also known is a granular solid preparation comprising tosufloxacin tosylate, sugar or sugar alcohol and a nonionic water-soluble cellulose derivative or polyvinyl alcohol (Patent Document 3).
  • tablets containing tosufloxacin tosylate are commercially available.
  • granular solid preparations and tablets are known.
  • a granular solid formulation is preferred.
  • the swallowing function develops like an elementary school student and the taste becomes clearer, tablets tend to be preferred.
  • the size of tablets greatly affects compliance. If it is too large, the child will not be able to swallow and compliance will be reduced. Since tablets for adults have a tablet diameter of 7.5 to 8.5 mm, which is large for children, there is a concern that the compliance of children will be reduced. Fine granules have been marketed as pediatric preparations containing tosufloxacin tosylate, but pediatric tablets have not been developed.
  • the dissolution rate after 5 minutes of the commercially available tablet containing tosufloxacin tosylate is 24%.
  • Tosufloxacin tosylate has a metal adhesion property, and when it is tableted, serious tableting failure (sticking) occurs in which the drug substance is fixed to the bag.
  • sticking serious tableting failure
  • An object of the present invention is to provide a tablet containing tosufloxacin tosylate which exhibits rapid dissolution, does not cause tableting troubles such as sticking, and is excellent in manufacturability.
  • the present inventors conducted intensive research. As a result, the tablet containing (1) tosufloxacin tosylate salt, (2) binder, and (3) acidic amino acid exhibits rapid dissolution, And it discovered that it was excellent in manufacturability, without causing a tableting trouble, and completed this invention.
  • the present invention provides the following.
  • a tablet comprising (1) tosufloxacin tosylate, (2) a binder, and (3) an acidic amino acid; the binder is selected from water-soluble polyvinyl polymers and gelatins Two or more tablets, wherein the content of the binder is less than 5% based on the tablet mass.
  • the acidic amino acid is L-aspartic acid.
  • the binder is a water-soluble polyvinyl polymer.
  • the disintegrant is one or more selected from carmellose, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropyl cellulose, crospovidone, sodium carboxymethyl starch and partially pregelatinized starch.
  • the tablet of description The tablet of description.
  • the present invention further provides the following.
  • [A] The tablet according to any one of [1] to [8], further comprising a fluidizing agent.
  • E The tablet according to [C] or [D], wherein the gelatin content is 0.1 to 4% based on the tablet mass.
  • a tablet comprising (1) tosufloxacin tosylate, (2) a binder, and (3) an acidic amino acid; the binder is a water-soluble polyvinyl polymer; the acidic amino acid is L
  • [G] A tablet comprising (1) tosufloxacin tosylate, (2) a binder, and (3) an acidic amino acid; the binder is polyvinyl alcohol; the acidic amino acid is L-aspartic acid Yes; The tablet according to [1], wherein the content of polyvinyl alcohol is 0.1 to 4% based on the weight of the tablet.
  • the tablet of the present invention is a tablet containing tosufloxacin tosylate which is easy to be taken by children and the like, exhibits quick dissolution, does not cause tableting troubles such as sticking, and is excellent in manufacturability.
  • the tablet of the present invention can also be a tablet having a secant for dose adjustment, and is useful as an antibacterial agent for children with improved compliance in children and the like.
  • the present invention is described in detail below. Unless otherwise specified,% used in the present specification means mass%.
  • the content rate of each component used in the present specification means the total content rate of a plurality of substances corresponding to each component unless there is a specific case when there are a plurality of substances corresponding to each component.
  • the “dissolution rate” used in the present specification means the dissolution rate measured according to the 16th revised Japanese Pharmacopoeia dissolution test method 2 (paddle method) unless otherwise specified.
  • the term “fast dissolution” used in the present specification means that the dissolution rate after 5 minutes from the start of the dissolution test is 60% or more.
  • the value of “60% or more” was obtained from tosufloxacin tosylate pediatric fine granules using the f2 function, which is an index of similarity of dissolution behavior.
  • it is more preferable that the dissolution rate 5 minutes after the start of the dissolution test is 73% or more.
  • the tablet of the present invention comprises tosufloxacin tosylate, a binder and an acidic amino acid.
  • the tablet of the present invention means an uncoated tablet and a film-coated tablet.
  • the film-coated tablet means a tablet obtained by coating a base tablet with a coating agent such as a polymer compound.
  • a film-coated tablet is preferable.
  • the tablet diameter is preferably 5.0 to 7.0 mm.
  • the dose and the number of doses can be appropriately selected according to the age, weight and symptoms of the patient, but the amount capable of exerting the drug effect is usually divided from once to several times a day. Can be administered. In general, 30 to 2000 mg of tosufloxacin may be administered in 1 to several divided doses a day.
  • Tosfloxacin tosylate used in the present invention can be produced, for example, by the method described in JP-B-63-020828.
  • Tosfloxacin tosylate used in the present invention includes hydrates, solvates and various forms of crystals and amorphous solids.
  • the tosufloxacin tosylate used in the present invention is preferably a hydrate.
  • the content of tosufloxacin tosylate is preferably 70% or less, more preferably 40 to 60%, relative to the tablet mass.
  • Examples of the binder used in the present invention include one or more selected from water-soluble polyvinyl polymers and gelatins, and water-soluble polyvinyl polymers are preferred.
  • the binder content may be less than 5%.
  • Examples of the water-soluble polyvinyl polymer include one or more selected from polyvinyl alcohol, polyvinyl pyrrolidone, and polyvinyl alcohol / polyethylene glycol / graft copolymer, preferably polyvinyl alcohol and polyvinyl pyrrolidone, and more preferably polyvinyl alcohol.
  • Examples of the polyvinyl alcohol include fully saponified polyvinyl alcohol and partially saponified polyvinyl alcohol, and partially saponified polyvinyl alcohol is preferred.
  • the content of the water-soluble polyvinyl polymer is preferably 0.01 to 4.5%, more preferably 0.05 to 4%, still more preferably 0.1 to 3% with respect to the tablet mass.
  • gelatins include one or two selected from alkali-treated gelatin and acid-treated gelatin, and alkali-treated gelatin is preferred.
  • the content of gelatin is preferably 0.1 to 4%, more preferably 0.3 to 4%, still more preferably 0.5 to 2% based on the tablet mass.
  • the acidic amino acid used in the present invention means an amino acid having two or more carboxyl groups in the molecule.
  • Examples of the acidic amino acid used in the present invention include one or two selected from aspartic acid and glutamic acid.
  • Preferable acidic amino acids include aspartic acid, and L-aspartic acid is more preferable.
  • the content of acidic amino acids is preferably 5 to 50%, more preferably 5 to 30%, still more preferably 10 to 20% based on the tablet mass.
  • the tablet of the present invention preferably further contains a disintegrant.
  • the disintegrant used in the present invention include one or two selected from carmellose, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropylcellulose, crospovidone, sodium carboxymethyl starch, and partially pregelatinized starch. More than species.
  • Preferred disintegrants include one or more selected from carmellose, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropylcellulose, crospovidone and carboxymethyl starch sodium.
  • Carmellose, low-substituted hydroxypropyl One or more selected from cellulose, crospovidone and sodium carboxymethyl starch are more preferred, and a combination of low-substituted hydroxypropylcellulose and crospovidone is more preferred.
  • Low-substituted hydroxypropyl cellulose is a low-substituted hydroxypropyl ether of cellulose, and the dried product contains hydroxypropoxy groups (—OC 3 H 6 OH: 75.09) 5.0 to 16.0% when quantified. .
  • the content of the disintegrant is preferably 5 to 50%, more preferably 5 to 30%, still more preferably 8 to 15% based on the tablet mass.
  • the tablet of the present invention preferably further contains a fluidizing agent.
  • the fluidizing agent include one or more selected from synthetic aluminum silicate, hydrous silicon dioxide, light anhydrous silicic acid, and the like, and one or two selected from hydrous silicon dioxide and light anhydrous silicic acid.
  • light anhydrous silicic acid is more preferable.
  • additives generally used for drugs can be used as long as the effects of the present invention are not impaired.
  • examples of the additive include excipients, lubricants, sweeteners, coloring agents, flavoring agents, surfactants, plasticizers and coating agents.
  • excipient examples include sugar alcohols such as erythritol, mannitol, xylitol and sorbitol; sugars such as sucrose, powdered sugar, lactose and glucose; ⁇ -cyclodextrin, ⁇ -cyclodextrin, ⁇ -cyclodextrin, hydroxypropyl Cyclodextrins such as ⁇ -cyclodextrin and sulfobutyl ether ⁇ -cyclodextrin sodium; celluloses such as crystalline cellulose and microcrystalline cellulose; starches such as corn starch, potato starch and pregelatinized starch; malonic acid and fumaric acid, etc.
  • sugar alcohols such as erythritol, mannitol, xylitol and sorbitol
  • sugars such as sucrose, powdered sugar, lactose and glucose
  • dicarboxylic acids One kind selected from dicarboxylic acids; oxycarboxylic acids such as glycolic acid, gluconic acid, tartaric acid, malic acid and citric acid; and organic acids having 2 to 6 carbon atoms such as ascorbic acid Others include two or more thereof.
  • Preferred excipients include sugar alcohols, and erythritol is more preferred.
  • the amount of the excipient used is not particularly limited, and an amount corresponding to the dosage form may be used.
  • Examples of the lubricant include one or more selected from stearic acid, magnesium stearate, calcium stearate, sodium stearyl fumarate, talc, sucrose fatty acid ester, and the like.
  • Examples of the sweetener include one or more selected from aspartame, saccharin, stevia, sucralose, thaumatin, and acesulfame potassium.
  • Examples of the colorant include one or more selected from titanium dioxide, iron sesquioxide, yellow iron sesquioxide, black iron oxide, edible red No. 102, edible yellow No. 4, edible yellow No. 5, and the like.
  • flavoring agents include essential oils such as orange oil, lemon oil, peppermint oil and pine oil; essences such as orange essence and peppermint essence; flavors such as cherry flavor, vanilla flavor and fruit flavor; apple micron, banana micron, One or two or more kinds selected from powder flavors such as peach micron, strawberry micron, and orange micron; vanillin; and ethyl vanillin.
  • the surfactant include one or more selected from sodium lauryl sulfate, dioctyl sodium sulfosuccinate, polysorbate, and polyoxyethylene hydrogenated castor oil.
  • plasticizer examples include one or more selected from triethyl citrate, dibutyl phthalate, macrogol (polyethylene glycol), triacetin, glycerol monocaprycaprate, lecithin, propylene glycol, and the like.
  • Examples of the coating agent include one or more selected from polymer compounds, plasticizers, colorants, lubricants, brighteners, and the like.
  • Examples of the polymer compound include one or more selected from hypromellose, hydroxypropyl cellulose, polyvinyl alcohol, polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, polyvinyl alcohol / polyethylene glycol / graft copolymer, and the like.
  • Examples of the lubricant used as the coating agent include talc.
  • Examples of the brightening agent include one or more selected from carnauba wax, white beeswax, beeswax and the like.
  • the amount of the polymer compound, plasticizer, colorant, lubricant and brightening agent used is not particularly limited, and a necessary amount may be appropriately blended depending on the purpose. These additives may be added either alone or in combination of two or more. The addition amount is not particularly limited, and an amount corresponding to the dosage form may be added.
  • a preferred tablet of the present invention is a tablet comprising (1) tosufloxacin tosylate, (2) a binder, and (3) an acidic amino acid; the binder is a water-soluble polyvinyl polymer; acidic An amino acid is L-aspartic acid; a tablet having a water-soluble polyvinyl polymer content of 0.01 to 4.5% based on the tablet mass.
  • Preferred water-soluble polyvinyl polymers are the same as described above.
  • a further preferred tablet of the present invention is a tablet comprising (1) tosufloxacin tosylate, (2) a binder, and (3) an acidic amino acid; the binder is polyvinyl alcohol; L-aspartic acid; a tablet having a polyvinyl alcohol content of 0.1 to 4% based on the tablet weight.
  • Preferred polyvinyl alcohol is the same as described above.
  • a preferred tablet of the present invention is a tablet comprising (1) tosufloxacin tosylate, (2) a binder, (3) an acidic amino acid, (4) a disintegrant, and (5) a fluidizing agent.
  • the binder is one or more selected from water-soluble polyvinyl polymers and gelatins; the acidic amino acid is L-aspartic acid; the disintegrant is crospovidone and / or carboxymethyl One or more containing sodium starch; the fluidizing agent is hydrous silicon dioxide or light anhydrous silicic acid; and the content of the binder is 0.1 to 3% of the tablet mass. .
  • binders selected from water-soluble polyvinyl polymers or gelatins and acidic amino acids are added to tosufloxacin tosylate, and further, an excipient, a fluid
  • a granulating powder is produced by a wet granulation method or a dry granulation method by adding an agent, a disintegrant and / or a sweetener. Subsequently, if necessary, an excipient, a fluidizing agent, a disintegrant and / or a lubricant can be added to the granulated powder to obtain a mixed powder for tableting, and tableting can be performed.
  • a film-coated tablet can be produced by a conventional method.
  • a preferable granulation method in the method for producing a granulated powder of the present invention includes a wet granulation method.
  • the wet granulation method include fluidized bed granulation method, rolling fluidized granulation method, centrifugal rolling granulation method, mixed stirring granulation method, high speed mixed stirring granulation method, rolling granulation method, wet crushing method Examples thereof include a granulation method and an extrusion granulation method.
  • Preferable wet granulation methods include fluidized bed granulation method, rolling fluidized granulation method, high speed mixing and stirring granulation method and wet crushing granulation method.
  • Fluidized bed granulation method and rolling fluidized granulation method include More preferred.
  • Alpha starch SWELSTAR WB-1 (Asahi Kasei Chemicals)
  • L-aspartic acid L-aspartic acid (Kyowa Hakko Bio)
  • Erythritol Erythritol T fine powder (Mitsubishi Chemical Foods)
  • Hydrous silicon dioxide Carplex # 80 (DSL.
  • Croscarmellose sodium Kikkolate (Asahi Kasei Chemicals) Crospovidone: Polyplusdon XL-10 (ISP) Light anhydrous silicic acid: Aerosil 200 (Japan Aerosil) Sucralose: Sucralose (P) (San-Eigen F.F.I.) Magnesium stearate: Magnesium stearate vegetable (Taihei Chemical Industry) Gelatin: Gelatin # 150 (Nitta Gelatin) Low-substituted hydroxypropyl cellulose: L-HPC LH-21 (Shin-Etsu Chemical) Hydroxypropyl cellulose: HPC-SL (Nippon Soda) Hydroxypropyl methylcellulose: TC-5E (Shin-Etsu Chemical) Polyvinyl alcohol (partially saponified product): EG-05PW (Nippon Synthetic Chemical Industry) Polyvinyl alcohol / polyethylene glycol / graft copolymer: Kolli
  • Tableting machine Tabflex TAB10 (Okada Seiko)
  • Rolling fluid granulating dryer Multiplex MP-01 (Paurek)
  • Test example 1 The uncoated tablets of Examples 1 to 25 and Comparative Examples 1 to 5 were used as test preparations.
  • (1) Dissolution test of preparation The standard value of dissolution is the dissolution rate 5 minutes after the start of dissolution test, which is similar to that of fast-dissolving children's fine granules, and the similarity of dissolution behavior. It was determined from the f2 function as an index, and was set based on the dissolution rate ⁇ 60% 5 minutes after the start of the dissolution test.
  • the dissolution test was conducted according to Method 16 (Paddle Method) of the 16th revised Japanese Pharmacopoeia. One tablet of each test preparation was added to 900 mL of water and stirred at 50 rpm.
  • the eluate was collected by an automatic sampling device and filtered through a filter having a pore size of 35 ⁇ m.
  • the concentration of tosufloxacin tosylate was measured according to UV-Vis absorbance measurement method ⁇ Japanese Pharmacopoeia General Test Method 2.24>.
  • Table 1 shows the formulation of the tablets with different binder types, the dissolution rate after 5 minutes, and the presence or absence of sticking.
  • the tablets of Examples 1 to 4 containing water-soluble polyvinyl polymer polyvinyl alcohol, polyvinyl pyrrolidone or polyvinyl alcohol / polyethylene glycol / graft copolymer (PVA / PEG graft copolymer) or gelatin as a binder are dissolved after 5 minutes. The rate was 75-82%, indicating rapid dissolution, and there was no sticking.
  • Comparative Examples 1 and 2 the tablets of Comparative Examples 1 and 2 containing hydroxypropylcellulose or hydroxypropylmethylcellulose as a binder had a dissolution rate of 82% and 80% after 5 minutes, respectively. As shown, it was a tablet whose score line and marking were unclear due to the occurrence of sticking.
  • the tablet of Comparative Example 3 containing pregelatinized starch as a binder was an uncoated tablet with a dissolution rate of 55% after 5 minutes and no fast dissolution, and the dividing line and markings were unclear due to the occurrence of sticking. Tablets containing a water-soluble polyvinyl polymer as a binder were excellent in dissolution and manufacturability.
  • Tables 2, 3 and 4 show the tablet formulations with varying amounts of binder used, the dissolution rate after 5 minutes and the presence or absence of sticking.
  • the tablets of Examples 5 to 13 containing polyvinyl alcohol as a binder showed fast dissolution with a dissolution rate of 63 to 84% after 5 minutes even when the amount of the binder was changed to 0.1 to 4%, and sticking There was no tablet, and the scored line and the engraved mark were clear tablets.
  • the binder is added at around 3%, but in the case of polyvinyl alcohol, excellent effects were observed in rapid dissolution and manufacturability even with a very small addition amount.
  • the tablet of Comparative Example 5 to which no binder was added showed a fast dissolution property with an elution rate of 82% after 5 minutes, but only tablets with unclear secant lines and markings were obtained due to the occurrence of sticking.
  • the tablets of Examples 2 and 14 containing polyvinyl pyrrolidone as the binder and the tablets of Examples 3 and 15 containing polyvinyl alcohol / polyethylene glycol / graft copolymer (PVA / PEG graft copolymer) as the binder are both Even when the amount was changed to 1% and 2%, the tablet showed quick dissolution, no sticking, and a tablet with clear score lines and markings.
  • Table 5 shows the formulation of the tablets with different amounts of gelatin used as the binder, the dissolution rate after 5 minutes, and the presence or absence of sticking.
  • the tablets of Examples 4, 16 and 17 having an amount of gelatin of 0.5 to 2% exhibit a fast dissolution property with a dissolution rate of 75 to 79% after 5 minutes, have no sticking, and have a clear dividing line and marking. Met.
  • Table 6 shows the formulations of tablets using polyvinyl alcohol as a binder and various disintegrants, the dissolution rate after 5 minutes, and the presence or absence of sticking.
  • the tablets of Examples 18 to 23 had a dissolution rate as fast as 62 to 80% after 5 minutes, had no sticking, and had clear dividing lines and markings.
  • the tablet of the present invention was excellent in rapid dissolution and manufacturability regardless of the type and combination of disintegrants.
  • Table 7 shows the formulation of the tablet using polyvinyl alcohol as a binder and changing the type or amount of the fluidizing agent, the dissolution rate after 5 minutes, and the presence or absence of sticking.
  • the tablet of Example 24 containing no fluidizing agent and the tablet of Example 25 containing hydrous silicon dioxide as the fluidizing agent showed fast dissolution properties of 62% and 74% after 5 minutes and no sticking
  • the score line and engraved mark were clear uncoated tablets. Since the preparation containing the fluidizing agent exhibits faster dissolution than the preparation containing no fluidizing agent, it is more preferable to include the fluidizing agent.
  • Example 1 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 33.0 g, light anhydrous silicic acid 8.0 g, low substituted hydroxypropylcellulose 12.0 g, crospovidone 8.0 g and sucralose 1.0 g were weighed. After passing through a sieve having an opening of 500 ⁇ m, the mixture was charged into a tumbling fluidized granulator and mixed. Thereafter, 200.0 g of a 1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • a 1% polyvinyl alcohol partially saponified product
  • Example 2 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 33.0 g, light anhydrous silicic acid 8.0 g, low substituted hydroxypropylcellulose 12.0 g, crospovidone 8.0 g and sucralose 1.0 g were weighed. After passing through a sieve having an opening of 500 ⁇ m, the mixture was charged into a tumbling fluidized granulator and mixed. Thereafter, 200.0 g of a 1% polyvinylpyrrolidone aqueous solution was sprayed for granulation, dried and sized to obtain a granulated powder.
  • Example 3 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 33.0 g, light anhydrous silicic acid 8.0 g, low substituted hydroxypropylcellulose 12.0 g, crospovidone 8.0 g and sucralose 1.0 g were weighed. After passing through a sieve having an opening of 500 ⁇ m, the mixture was charged into a tumbling fluidized granulator and mixed. Thereafter, 200.0 g of a 1% polyvinyl alcohol / polyethylene glycol / graft copolymer aqueous solution was sprayed and granulated, dried and sized to obtain a granulated powder.
  • Example 4 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 33.0 g, light anhydrous silicic acid 8.0 g, low substituted hydroxypropylcellulose 12.0 g, crospovidone 8.0 g and sucralose 1.0 g were weighed. After passing through a sieve having an opening of 500 ⁇ m, the mixture was charged into a tumbling fluidized granulator and mixed. Thereafter, 200.0 g of a 1% gelatin aqueous solution was sprayed to granulate, dried and sized to obtain a granulated powder.
  • Example 5 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 34.8 g, light anhydrous silicic acid 8.0 g, low substituted hydroxypropylcellulose 12.0 g, crospovidone 8.0 g and sucralose 1.0 g were weighed. After passing through a sieve having an opening of 500 ⁇ m, the mixture was charged into a tumbling fluidized granulator and mixed. Thereafter, 200.0 g of 0.1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • 0.1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • Example 6 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 34.6 g, light anhydrous silicic acid 8.0 g, low substituted hydroxypropylcellulose 12.0 g, crospovidone 8.0 g and sucralose 1.0 g were weighed. After passing through a sieve having an opening of 500 ⁇ m, the mixture was charged into a tumbling fluidized granulator and mixed. Thereafter, 200.0 g of 0.2% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • polyvinyl alcohol partially saponified product
  • Example 7 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 34.0 g, light anhydrous silicic acid 8.0 g, low substituted hydroxypropylcellulose 12.0 g, crospovidone 8.0 g and sucralose 1.0 g were weighed. After passing through a sieve having an opening of 500 ⁇ m, the mixture was charged into a tumbling fluidized granulator and mixed. Thereafter, 200.0 g of 0.5% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • polyvinyl alcohol partially saponified product
  • Example 8 Tosfloxacin tosylate hydrate 7.50 g, L-aspartic acid 2.25 g, erythritol 2.50 g, hydrous silicon dioxide 0.30 g, low-substituted hydroxypropylcellulose 1.50 g and polyvinyl alcohol (partially saponified product) 0.29 g were weighed. After sieving with an opening 500 ⁇ m sieve, they were mixed. The powder was put in a mortar, granulated while adding water, sized with a sieve having an opening of 850 ⁇ m, dried, and further sized with a sieve having an opening of 500 ⁇ m to obtain a granulated powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm and a round uncoated tablet having a score line and a stamp of 117 mg per tablet.
  • Example 9 Tosfloxacin tosylate hydrate 7.50 g, L-aspartic acid 2.25 g, erythritol 2.50 g, hydrous silicon dioxide 0.30 g, low-substituted hydroxypropylcellulose 1.50 g and polyvinyl alcohol (partially saponified product) 0.44 g were weighed. After sieving with an opening 500 ⁇ m sieve, they were mixed. The powder was put in a mortar, granulated while adding water, sized with a sieve having an opening of 850 ⁇ m, dried, and further sized with a sieve having an opening of 500 ⁇ m to obtain a granulated powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm and a round uncoated tablet having a score line and an inscription of 118 mg per tablet.
  • Example 10 Tosfloxacin tosylate hydrate 7.50 g, L-aspartic acid 2.25 g, erythritol 2.50 g, hydrous silicon dioxide 0.30 g, low substituted hydroxypropylcellulose 1.50 g and polyvinyl alcohol (partially saponified product) 0.59 g were weighed. After sieving with an opening 500 ⁇ m sieve, they were mixed. The powder was put in a mortar, granulated while adding water, sized with a sieve having an opening of 850 ⁇ m, dried, and further sized with a sieve having an opening of 500 ⁇ m to obtain a granulated powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm, and a round uncoated tablet having a score line of 120 mg per tablet and an inscription was obtained.
  • Example 11 Tosfloxacin tosylate hydrate 7.50 g, L-aspartic acid 2.25 g, erythritol 2.33 g, light anhydrous silicic acid 0.6 g, low substituted hydroxypropylcellulose 0.9 g, crospovidone 0.6 g, polyvinyl alcohol (partially saponified product) 0.3 g And 0.075 g of sucralose was weighed, sieved with a sieve having an opening of 500 ⁇ m, and mixed.
  • the powder was put in a mortar, granulated while adding water, sized with a sieve having an opening of 850 ⁇ m, dried, and further sized with a sieve having an opening of 500 ⁇ m to obtain a granulated powder.
  • 0.5% equivalent of light anhydrous silicic acid and 2.5% equivalent of magnesium stearate were added through a sieve having an opening of 500 ⁇ m and mixed to obtain a tableted powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm, and a round uncoated tablet having a score line of 120 mg per tablet and an inscription was obtained.
  • Example 12 Tosfloxacin tosylate hydrate 7.50g, L-aspartic acid 2.25g, erythritol 2.18g, light anhydrous silicic acid 0.6g, low substituted hydroxypropylcellulose 0.9g, crospovidone 0.6g, polyvinyl alcohol (partially saponified product) 0.45g And 0.075 g of sucralose was weighed, sieved with a sieve having an opening of 500 ⁇ m, and mixed. The powder was put in a mortar, granulated while adding water, sized with a sieve having an opening of 850 ⁇ m, dried, and further sized with a sieve having an opening of 500 ⁇ m to obtain a granulated powder.
  • Example 13 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 27.0 g, light anhydrous silicic acid 8.0 g, low substituted hydroxypropylcellulose 12.0 g, crospovidone 8.0 g and sucralose 1.0 g were weighed. After passing through a sieve having an opening of 500 ⁇ m, the mixture was charged into a tumbling fluidized granulator and mixed. Thereafter, 200.0 g of a 4% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and sized to obtain a granulated powder.
  • a 4% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and sized to obtain a granulated powder.
  • Example 14 Tosfloxacin tosylate hydrate 7.50 g, L-aspartic acid 2.25 g, erythritol 2.50 g, hydrous silicon dioxide 0.30 g, low-substituted hydroxypropylcellulose 1.50 g, polyvinylpyrrolidone 0.29 g were weighed and sieved with 500 ⁇ m mesh After sieving, they were mixed. The powder was put in a mortar, granulated while adding water, sized with a sieve having an opening of 850 ⁇ m, dried, and further sized with a sieve having an opening of 500 ⁇ m to obtain a granulated powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm and a round uncoated tablet having a score line and a stamp of 117 mg per tablet.
  • Example 15 Tosfloxacin tosylate hydrate 7.50 g, L-aspartic acid 2.25 g, erythritol 2.50 g, hydrous silicon dioxide 0.30 g, low substituted hydroxypropylcellulose 1.50 g, polyvinyl alcohol / polyethylene glycol / graft copolymer 0.29 g, The mixture was sieved with a sieve having an opening of 500 ⁇ m and mixed. The powder was put in a mortar, granulated while adding water, sized with a sieve having an opening of 850 ⁇ m, dried, and further sized with a sieve having an opening of 500 ⁇ m to obtain a granulated powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm and a round uncoated tablet having a score line and a stamp of 117 mg per tablet.
  • Example 16 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 34.0 g, light anhydrous silicic acid 8.0 g, low substituted hydroxypropylcellulose 12.0 g, crospovidone 8.0 g and sucralose 1.0 g were weighed. After passing through a sieve having an opening of 500 ⁇ m, the mixture was charged into a tumbling fluidized granulator and mixed. Thereafter, 200.0 g of 0.5% gelatin aqueous solution was sprayed to granulate, dried and sized to obtain a granulated powder.
  • Example 17 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 31.0 g, light anhydrous silicic acid 8.0 g, low substituted hydroxypropylcellulose 12.0 g, crospovidone 8.0 g and sucralose 1.0 g were weighed. After passing through a sieve having an opening of 500 ⁇ m, the mixture was charged into a tumbling fluidized granulator and mixed. Thereafter, 200.0 g of a 2% gelatin aqueous solution was sprayed to granulate, dried and sized to obtain a granulated powder.
  • Example 18 Weigh 100.0 g of tosufloxacin tosylate hydrate, 30.0 g of L-aspartic acid, 32.0 g of erythritol, 10.0 g of light anhydrous silicic acid, 10.0 g of carmellose and 10.0 g of low-substituted hydroxypropylcellulose, and use a sieve with an opening of 500 ⁇ m. After sieving, it was charged into a rolling fluidized granulator and mixed. Thereafter, 300.0 g of 0.67% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and sized to obtain a granulated powder.
  • polyvinyl alcohol partially saponified product
  • magnesium stearate equivalent to 3.0% relative to the weight of the uncoated tablet was added through a sieve having an opening of 180 ⁇ m and mixed to obtain a tableted powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm, and a round uncoated tablet having a score line of 120 mg per tablet and an inscription was obtained.
  • Example 19 Tosufloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 32.0 g, light anhydrous silicic acid 10.0 g, carmellose 10.0 g and crospovidone 10.0 g were weighed, sieved with a sieve with an opening of 500 ⁇ m, The mixture was charged into a dynamic fluidized granulator and mixed. Thereafter, 300.0 g of 0.67% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and sized to obtain a granulated powder.
  • polyvinyl alcohol partially saponified product
  • magnesium stearate equivalent to 3.0% relative to the weight of the uncoated tablet was added through a sieve having an opening of 180 ⁇ m and mixed to obtain a tableted powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm, and a round uncoated tablet having a score line of 120 mg per tablet and an inscription was obtained.
  • Example 20 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 32.0 g, light anhydrous silicic acid 10.0 g, low-substituted hydroxypropylcellulose 10.0 g and crospovidone 10.0 g were weighed and sieved with an opening of 500 ⁇ m After sieving, it was charged into a rolling fluidized granulator and mixed. Thereafter, 300.0 g of 0.67% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and sized to obtain a granulated powder.
  • polyvinyl alcohol partially saponified product
  • magnesium stearate equivalent to 3.0% relative to the weight of the uncoated tablet was added through a sieve having an opening of 180 ⁇ m and mixed to obtain a tableted powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm, and a round uncoated tablet having a score line of 120 mg per tablet and an inscription was obtained.
  • Example 21 Tosufloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 32.0 g, light anhydrous silicic acid 10.0 g and low-substituted hydroxypropylcellulose 20.0 g were weighed, sieved with a sieve having an opening of 500 ⁇ m, The mixture was charged into a dynamic fluidized granulator and mixed. Thereafter, 200.0 g of a 1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • a 1% polyvinyl alcohol partially saponified product
  • magnesium stearate equivalent to 3.0% relative to the weight of the uncoated tablet was added through a sieve having an opening of 180 ⁇ m and mixed to obtain a tableted powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm, and a round uncoated tablet having a score line of 120 mg per tablet and an inscription was obtained.
  • Example 22 Tosufloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 32.0 g, light anhydrous silicic acid 10.0 g and croscarmellose sodium 20.0 g were weighed, passed through a sieve with an opening of 500 ⁇ m, and tumbling flow Charged into a granulator and mixed. Thereafter, 200.0 g of a 1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • a 1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • magnesium stearate equivalent to 3.0% relative to the weight of the uncoated tablet was added through a sieve having an opening of 180 ⁇ m and mixed to obtain a tableted powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm, and a round uncoated tablet having a score line of 120 mg per tablet and an inscription was obtained.
  • Example 23 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 32.0 g, light anhydrous silicic acid 10.0 g and carboxymethyl starch sodium 20.0 g were weighed, sieved through a sieve with an opening of 500 ⁇ m, and tumbling flow Charged into a granulator and mixed. Thereafter, 200.0 g of a 1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • a 1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • magnesium stearate equivalent to 3.0% relative to the weight of the uncoated tablet was added through a sieve having an opening of 180 ⁇ m and mixed to obtain a tableted powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm, and a round uncoated tablet having a score line of 120 mg per tablet and an inscription was obtained.
  • Example 24 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 43.3 g, carmellose 10.0 g, and crospovidone 10.0 g were weighed, passed through a sieve with an opening of 500 ⁇ m, and then put into a tumbling fluid granulator and dryer. Charged and mixed. Thereafter, 200.0 g of a 1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • a 1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • Example 25 Tosfloxacin tosylate hydrate 100.0 g, L-aspartic acid 30.0 g, erythritol 33.3 g, hydrous silicon dioxide 10.0 g, carmellose 10.0 g and crospovidone 10.0 g were weighed, sieved with a sieve with an opening of 500 ⁇ m, and rolled. The mixture was charged into a fluidized granulator and mixed. Thereafter, 200.0 g of a 1% polyvinyl alcohol (partially saponified product) aqueous solution was sprayed and granulated, dried and granulated to obtain a granulated powder.
  • a 1% polyvinyl alcohol partially saponified product
  • Example 26 On the uncoated tablet of Example 5, using a tablet coating machine (DRC-200, manufactured by Paulek), a coating agent (OPADRY 00F440000, Nippon Colorcon GK: Hypromellose 2910 71.500%, Macrogol 6000 14.166%, Talc 7.167%, Titanium oxide 7.067%, ferric sesquioxide 0.100% dispersed in water) was coated at a rate of 4 mg per tablet to obtain 124 mg film-coated tablets per tablet.
  • DRC-200 tablet coating machine
  • a coating agent OPC-200, manufactured by Paulek
  • Example 27 The uncoated tablets of Example 6 were coated in the same manner as in Example 26 to obtain 124 mg of film-coated tablets per tablet.
  • Example 28 The uncoated tablets of Example 7 were coated in the same manner as in Example 26 to obtain 124 mg of film-coated tablets per tablet.
  • Example 29 The uncoated tablets of Example 1 were coated in the same manner as in Example 26 to obtain 124 mg film-coated tablets per tablet.
  • Example 30 The uncoated tablets of Example 13 were coated in the same manner as in Example 26 to obtain 124 mg film-coated tablets per tablet.
  • a light silicic acid equivalent to 0.5% of the uncoated tablet mass is added to the granulated powder through a sieve having an opening of 500 ⁇ m, and magnesium stearate equivalent to 2.5% of the uncoated tablet mass is added to a sieve having an opening of 180 ⁇ m. And mixed to obtain a tableting powder.
  • This tableting powder was compression-molded with a tableting machine using a tablet with a tablet diameter of 6.5 mm, and a round uncoated tablet having a score line of 120 mg per tablet and an inscription was obtained.
  • the tablet of the present invention is useful as an antibacterial agent for children with improved compliance for children.

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  • Life Sciences & Earth Sciences (AREA)
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  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Inorganic Chemistry (AREA)
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Abstract

Ce comprimé contient (1) de la tosufloxacine tosilate, (2) un liant et (3) un acide aminé acide. Le comprimé contient un ou plusieurs types de liant choisis parmi des polymères polyvinyliques solubles dans l'eau et des gélatines, et est utile en tant que comprimé contenant de la tosufloxacine tosilate qui présente une dissolution rapide, n'est pas sujet à des problèmes de formation de comprimés, et peut être fabriqué de manière stable.
PCT/JP2017/016681 2016-04-27 2017-04-27 Comprimé contenant de la tosufloxacine tosilate WO2017188361A1 (fr)

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Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6272616A (ja) * 1985-09-27 1987-04-03 Toyama Chem Co Ltd 抗菌剤
JP2007510001A (ja) * 2003-11-04 2007-04-19 バイエル・ヘルスケア・アクチェンゲゼルシャフト 薬剤特性が改善された矯味物質を含有する薬剤製剤
JP2007269783A (ja) * 2006-03-06 2007-10-18 Toyama Chem Co Ltd トシル酸トスフロキサシンを含有する粒状固形製剤
JP2008150364A (ja) * 2006-11-20 2008-07-03 Daiichi Sankyo Co Ltd レボフロキサシン含有錠剤
JP2009089982A (ja) * 2007-10-11 2009-04-30 Ohara Yakuhin Kogyo Kk 打錠用造粒物の造粒方法
JP2009269874A (ja) * 2008-05-09 2009-11-19 Daido Kasei Kogyo Kk 水性液剤
JP2010013402A (ja) * 2008-07-04 2010-01-21 Nof Corp 打錠用被覆造粒剤
JP2011026312A (ja) * 2009-06-30 2011-02-10 Kowa Co アスパラギン酸又はその塩含有固形製剤
JP2013147470A (ja) * 2012-01-20 2013-08-01 Nipro Corp 口腔内崩壊錠
JP2013231090A (ja) * 2013-08-23 2013-11-14 Toyama Chem Co Ltd トスフロキサシンおよびポリビニルピロリドンを含有する粒状固形製剤
CN106176646A (zh) * 2016-08-19 2016-12-07 珠海同源药业有限公司 一种甲苯磺酸妥舒沙星分散片及其制备方法

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6272616A (ja) * 1985-09-27 1987-04-03 Toyama Chem Co Ltd 抗菌剤
JP2007510001A (ja) * 2003-11-04 2007-04-19 バイエル・ヘルスケア・アクチェンゲゼルシャフト 薬剤特性が改善された矯味物質を含有する薬剤製剤
JP2007269783A (ja) * 2006-03-06 2007-10-18 Toyama Chem Co Ltd トシル酸トスフロキサシンを含有する粒状固形製剤
JP2008150364A (ja) * 2006-11-20 2008-07-03 Daiichi Sankyo Co Ltd レボフロキサシン含有錠剤
JP2009089982A (ja) * 2007-10-11 2009-04-30 Ohara Yakuhin Kogyo Kk 打錠用造粒物の造粒方法
JP2009269874A (ja) * 2008-05-09 2009-11-19 Daido Kasei Kogyo Kk 水性液剤
JP2010013402A (ja) * 2008-07-04 2010-01-21 Nof Corp 打錠用被覆造粒剤
JP2011026312A (ja) * 2009-06-30 2011-02-10 Kowa Co アスパラギン酸又はその塩含有固形製剤
JP2013147470A (ja) * 2012-01-20 2013-08-01 Nipro Corp 口腔内崩壊錠
JP2013231090A (ja) * 2013-08-23 2013-11-14 Toyama Chem Co Ltd トスフロキサシンおよびポリビニルピロリドンを含有する粒状固形製剤
CN106176646A (zh) * 2016-08-19 2016-12-07 珠海同源药业有限公司 一种甲苯磺酸妥舒沙星分散片及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KATSUHIDE TERADA, FORMULATION DESIGN AND PHYSICOCHEMICAL CHARACTERIZATION FOR PHARMACEUTICAL EXCIPIENTS, January 2016 (2016-01-01), pages 6 *

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