WO2009128543A1 - Procédé de fabrication d'un comprimé contenant de la silice, comprimé et particule composite pour le comprimé - Google Patents

Procédé de fabrication d'un comprimé contenant de la silice, comprimé et particule composite pour le comprimé Download PDF

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Publication number
WO2009128543A1
WO2009128543A1 PCT/JP2009/057792 JP2009057792W WO2009128543A1 WO 2009128543 A1 WO2009128543 A1 WO 2009128543A1 JP 2009057792 W JP2009057792 W JP 2009057792W WO 2009128543 A1 WO2009128543 A1 WO 2009128543A1
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Prior art keywords
tablet
silica
drug
tablets
excipient
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PCT/JP2009/057792
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English (en)
Japanese (ja)
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洋文 竹内
洋平 帆足
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ニプロ株式会社
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Priority to JP2010508265A priority Critical patent/JPWO2009128543A1/ja
Publication of WO2009128543A1 publication Critical patent/WO2009128543A1/fr

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    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/10—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic in stationary drums or troughs, provided with kneading or mixing appliances

Definitions

  • the present invention relates to a method for producing a tablet containing silica. Furthermore, the present invention extends to tablet-containing composite particles for producing tablets, and tablets containing silica produced by the production method.
  • Patent Document 1 discloses that the drug elution can be improved by blending silica as a dispersant.
  • the problem of the tablet of Patent Document 1 is that the hardness of the tablet to be produced is low.
  • Patent Document 2 solves the problem of Patent Document 1 by manufacturing including a step of previously combining silica and one or more components other than silica to form composite particles.
  • a technique is disclosed in which the hardness of a manufactured tablet is improved by combining an excipient with silica.
  • the compounding in Patent Document 1 is mainly performed by a spray drying method.
  • the spray drying method is a method of producing by spraying a liquid in which silica or one or more components other than silica are dissolved or dispersed in some solvent.
  • a liquid in which silica or one or more components other than silica are dissolved or dispersed in some solvent when compositing silica, (1) prepare a solution in which one or more components other than silica and silica are dissolved or dispersed in some solvent, and (2) dry the solvent in the solution sprayed with silica. 2 steps are performed. For this reason, there are many problems in that the number of manufacturing steps for complexing silica is high and the manufacturing cost is high.
  • the solvent used is not water but an organic solvent.
  • further problems such as toxicity problems due to the remaining organic solvent and environmental load may be caused.
  • An object of the present invention is to provide a method for producing a tablet containing silica containing silica that is simple and inexpensive to produce.
  • the solution to the problem in the prior art of the present invention is the following tablet manufacturing method.
  • the production method of the present invention includes [1] a step of obtaining composite particles for tablets by kneading silica and a melted drug or an excipient other than silica and returning to normal temperature.
  • the number of manufacturing steps for compounding silica is only one.
  • Silica refers to an inorganic compound called silicon dioxide under the IUPAC name and also called quartz or silicic anhydride.
  • the shape of the silica used in the production method of the present invention is preferably a powder or a particle having a particle diameter smaller than that of the powder.
  • the quality of the silica is preferably a pharmaceutical additive standard compliant grade. Examples of such silica include Cylicia (registered trademark) series manufactured by Fuji Silysia Chemical Ltd. and Aerosil (registered trademark) manufactured by Degussa.
  • Silica is preferably porous from the viewpoint of easy compounding. Examples of the commercially available porous silica include Silicia (registered trademark) series manufactured by Fuji Silysia Chemical Ltd.
  • the tablet component kneaded with silica is a drug or an excipient.
  • silica and a drug are kneaded, the dissolution property of the drug in the manufactured tablet is improved.
  • fillers other than a silica the hardness of the manufactured tablet improves. That is, those skilled in the art can determine the tablet components to be kneaded with silica according to the drug or excipient used.
  • the drug may be a compound that can be formulated into a tablet, and is not particularly limited as long as it is an individual at room temperature.
  • examples of such drugs include indomethacin, fenofibrate, acetaminophen, famotidine, cimetidine, ranitidine hydrochloride, roxatidine acetate, nizatidine, lafutidine, omeprazole, omeprazole sodium, lansoprazole, rabeprazole sodium, pirenzepine hydrochloride, proglumide , Ugastron, phenytoin, phenobarbital, phenobarbital sodium, primidone, sodium valproate, carbamazepine, trimethadione, Zomig, granisetron hydrochloride, azesetron hydrochloride, ondasetron hydrochloride, ramosetron hydrochloride, tropisetron hydrochloride, triazolam
  • Excipients other than silica refer to tablet components other than silica that are added so as to be an appropriate amount for handling as a tablet when the effective amount of the drug in the tablet is small, and refers to those having no physiological activity.
  • Excipients other than silica may be any compound that can be formulated into tablets, and are not particularly limited as long as they are solid at room temperature. Examples of such excipients include sugar alcohols such as mannitol, erythritol, sorbitol, xylitol, trehalose, maltitol and lactitol, and crystalline cellulose, powdered cellulose, hydroxypropylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose and ethylcellulose. And the like.
  • the silica described above corresponds to a so-called excipient, but an excipient other than silica is added to improve tablet hardness in the tablet produced as described above.
  • the above-mentioned drugs or excipients other than silica are kneaded with silica in a melted or crystal hydrated state.
  • the temperature condition for melting it is desirable to be near the melting point.
  • the drug when it is indomethacin, it may be around 155 degrees, and when the drug is fenofibrate, it may be around 80 degrees.
  • the excipient when the excipient is mannitol, it may be around 166 degrees, when the excipient is erythritol, around 121.5 degrees, and when the excipient is trehalose, it may be around 97 degrees.
  • the temperature condition in the kneading may be slightly lower than the melting point of the excipient other than the drug or silica. If this temperature condition is expressed qualitatively, it means a condition equal to or higher than the temperature at which the endotherm attributed to the melting point in differential scanning calorimetry (DSC) of excipients other than drugs or silica begins.
  • DSC differential scanning calorimetry
  • crystal hydration is a case where excipients other than the drug or silica have water of crystallization, and the excipient other than drug or silica dissolves in the crystal water as the temperature rises.
  • Crystal hydration is preferably in a state where all of the excipients other than the drug or silica are dissolved in water of crystallization, but a partially dissolved state is also included in the crystal hydration in the present invention.
  • the temperature condition in crystal hydration is expressed qualitatively, it means a condition equal to or higher than the temperature at which the endotherm attributed to the melting point of crystal water in differential scanning calorimetry (DSC) starts.
  • DSC differential scanning calorimetry
  • Kneading is performed, for example, by a method according to the stirring granulation method, rolling granulation method, and extrusion granulation method.
  • An excipient other than the drug or silica is melted or crystal hydrated and kneaded.
  • the method according to the stirring granulation method, the rolling granulation method and the extrusion granulation method is a granulation apparatus that enables these granulation methods, as long as it has a mechanism capable of heating the apparatus. It is not limited.
  • the silica and the drug or excipients other than silica are granulated by returning to normal temperature.
  • the granulated silica and drug or excipient other than silica are combined with silica as a base material with the drug or excipient other than silica adsorbed around the silica.
  • the granulated particles are referred to as “composite particles for tablets”.
  • poorly water-soluble drug examples include indomethacin and fenofibrate.
  • poorly water-soluble in the present invention refers to a drug having a solubility in water of 1 mg / mL or less.
  • the remaining of the organic solvent in the tablet does not become a problem, which is why a poorly water-soluble drug is mentioned as a desirable drug. .
  • sugar alcohol is preferable from the viewpoint of being a low-molding excipient and applicable to orally disintegrating tablets, and mannitol, erythritol, and trehalose are more preferable.
  • the apparatus for the agitation granulation method is preferable from the viewpoint that the apparatus is small.
  • mixer-type devices and screw-type devices for the stirring granulation method.
  • the former apparatus include a Pugmill mixer, a Henschel mixer, and an Eirich (registered trademark) mixer.
  • the latter device include a uniaxial device and a biaxial device.
  • a screw type biaxial one (biaxial kneader) is preferable.
  • the biaxial kneader include the KRC (registered trademark) series manufactured by Kurimoto Steel Works.
  • the kneading time is not particularly limited because it depends on the size of the apparatus, but it is about 1 to 10 minutes.
  • the present invention also extends to composite particles for tablets produced by kneading [6] silica with a melted or crystal hydrated drug or an excipient other than silica and returning to normal temperature.
  • the steps up to obtaining composite particles for tablets are as described above.
  • This composite particle for tablets can be used as a tablet component for producing a tablet.
  • the present invention provides [7] silica, a melted or crystal hydrated drug, or an excipient other than silica to knead to obtain composite particles for tablets, and the composite particles for tablets and other tablet components It extends to tablets produced by mixing and tableting. The steps up to obtaining composite particles for tablets are as described above.
  • the manufacture of a tablet using the above-described composite particle for tablets is easily performed by mixing the composite particles for tablet and other tablet components, and tableting.
  • tablet components include excipients, disintegrants, binders, solubilizers, lubricants, fragrances, foaming agents, surfactants, pH adjusters, preservatives, and coloring agents.
  • the present invention is not limited by the types of these additives.
  • Such other tablet components are appropriately selected by those skilled in the art as long as they do not affect the drug efficacy of the active ingredient.
  • the disintegrant is preferably used.
  • excipients are no different from those combined with silica described above. It should be noted that the excipients as other tablet components mentioned here are used even when the excipient is used as a composite with the above-mentioned silica. It means you may do it. The excipient as the other tablet component may be the same or different from the excipient complexed with the silica described above.
  • Disintegrants include, for example, crospovidone, sodium carboxy starch, sodium carboxymethyl starch, starch, partially pregelatinized starch, corn starch, lactose, calcium carbonate, precipitated calcium carbonate, calcium citrate, synthetic aluminum silicate, low substituted hydroxy
  • examples include propylcellulose, croscarmellose, croscarmellose sodium, carboxymethylcellulose calcium, carmellose and hydroxypropyl starch. The present invention is not limited to the types of these disintegrants.
  • binders examples include gelatin, agar, alginic acid, sodium alginate, dextrin, chitansan gum, gum arabic powder, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, partially saponified polyvinyl alcohol, methylcellulose, pullulan, and partially pregelatinized.
  • examples include starch and saccharides. The present invention is not limited to these binder types.
  • solubilizer examples include magnesium oxide, calcium oxide, sodium citrate, magnesium chloride, sodium carbonate, and sodium hydrogen carbonate.
  • the present invention is not limited to these types of solubilizers.
  • lubricants examples include magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, polyethylene glycol, stearic acid, light anhydrous silicic acid, hydrogenated rapeseed oil, hydrogenated castor oil, glycerin fatty acid ester, sodium stearyl fumarate, benzoic acid Examples include sodium acid, L-leucine and L-valine. The present invention is not limited to these types of lubricants.
  • fragrances include mint, lemon and orange.
  • the present invention is not limited to these types of fragrances.
  • foaming agent examples include tartrate, citrate and bicarbonate.
  • the present invention is not limited to these types of foaming agents.
  • surfactant examples include anionic surfactants such as sodium alkyl sulfate, nonionic surfactants such as sucrose fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, and polyoxyethylene castor oil derivative. Agents and the like. The present invention is not limited to these surfactant types.
  • pH adjuster examples include inorganic salts such as sodium hydrogen carbonate, calcium hydrogen phosphate and sodium hydrogen phosphate, organic acids such as glycine, acetic acid, succinic acid, tartaric acid, fumaric acid and citric acid, or salts of these organic acids. Etc.
  • the present invention is not limited to these types of pH adjusters.
  • preservative examples include benzoic acid, paraoxybenzoic acid and salts thereof.
  • the present invention is not limited to these types of preservatives.
  • colorant examples include yellow iron oxide, yellow ferric oxide, ferric oxide (red), orange essence, brown iron oxide, caramel, light anhydrous silicic acid, edible blue No. 5, edible yellow No. 4, and edible yellow 4 No. aluminum lake, edible yellow No. 5, edible red No. 2, edible red No. 3, edible red No. 102, talc, sodium fluorescein, green tea powder, vitamin C and the like.
  • the present invention is not limited to these types of colorants.
  • the mixing of the composite particles for tablets and other tablet components can be performed, for example, by using an apparatus such as a V-type mixer or a container blender. Thereby, the mixture of the composite particle for tablets and other tablet components is obtained.
  • the present invention is not limited by these mixing techniques.
  • a tableting device for example, a tableting mortar used for tablet molding, an upper punch and a lower punch for tableting, a hydraulic hand press machine, a single-shot tableting machine, a rotary tableting machine, etc. Can be used.
  • the present invention is not limited by these tableting techniques.
  • the shape of the tablet is not particularly limited because it is a matter appropriately designed by those skilled in the art.
  • the shape may be a disk shape, a donut shape, a polygonal plate shape, a spherical shape, an elliptical shape, a caplet shape, or the like.
  • the shape is preferably a disc shape which is a normal tablet shape.
  • the size of the orally disintegrating tablet is not particularly limited because it is a matter appropriately designed by those skilled in the art. However, it is suitable to be slightly larger so as not to be swallowed directly, and for example, it is preferable that the diameter is about 3 to 30 mm and the thickness is about 1 to 10 mm.
  • the production method of the present invention is simpler and less expensive to manufacture because the number of steps in the composite of silica is reduced as compared with the conventional production method.
  • an inexpensive tablet composite particle and a tablet using the tablet composite particle can be provided.
  • an organic solvent is not used. It can also be provided. Thereby, the safer composite particle for tablets and the composite particle for tablets can be provided.
  • silica porous silica powder (trade name: Silicia 350, Fuji Silysia Ltd.) was used.
  • indomethacin commercially available product
  • the porous silica powder and indomethacin are kneaded at a weight ratio of 1: 1 using a twin-screw kneader (trade name: KRC Jr., Kurimoto Seiko) at a temperature of 160 ° C. near the melting point of indomethacin. It was. Thereby, composite particles for tablets were obtained.
  • Example 1 The composite particles for tablets obtained in Example 1 and the indomethacin bulk powder of Comparative Example 1 were subjected to a dissolution test according to the Japanese Pharmacopoeia General Test Method Dissolution Test Method (Paddle Method, 50 rpm).
  • the Japanese Pharmacopoeia General Test Method Disintegration Test Method Second Solution pH 6.8 was used, and the measurement was performed by the ultraviolet-visible absorbance measurement method (measurement wavelength: 320 nm).
  • the test results are shown in FIG.
  • the dissolution properties of indomethacin from tablet composite particles were greatly improved compared to the indomethacin bulk powder.
  • silica porous silica powder (trade name: Silicia 350, Fuji Silysia Ltd.) was used. Moreover, fenofibrate (commercially available product), which is a poorly water-soluble drug, was used as a drug kneaded with silica or an excipient other than silica.
  • the porous silica powder and fenofibrate are kneaded at a weight ratio of 1: 1 using a twin-screw kneader (trade name: KRC Jr., Kurimoto Seiko) at a temperature of about 80 ° C. near the melting point of fenofibrate. I went. Thereby, composite particles for tablets were obtained.
  • Example 2 The composite particles for tablets obtained in Example 2 and the fenofibrate bulk powder of Comparative Example 2 were subjected to a dissolution test according to the Japanese Pharmacopoeia General Test Method Dissolution Test Method (Paddle Method, 50 rpm). A 0.1M sodium lauryl sulfate solution was used as a test solution, and measurement was performed by an ultraviolet-visible absorbance measurement method (measurement wavelength: 290 nm). The test results are shown in FIG. The dissolution properties of fenofibrate from the tablet composite particles were greatly improved compared to the fenofibrate bulk powder.
  • silica porous silica powder (trade name: Silicia 350, Fuji Silysia Ltd.) was used. Moreover, erythritol (commercially available product) was used as a drug to be kneaded with silica or an excipient other than silica. The porous silica powder and erythritol are kneaded at a weight ratio of 1: 2, using a twin-screw kneader (trade name: KRC Jr., Kurimoto Seiko) at a temperature of 120 ° C. near the melting point of erythritol. It was. Thereby, composite particles for tablets were obtained.
  • a twin-screw kneader trade name: KRC Jr., Kurimoto Seiko
  • the composite particles for tablets and other tablet components were mixed and tableted to produce tablets.
  • erythritol excipient as another tablet component
  • magnesium stearate lubricant
  • Erythritol is mixed with 10% by weight of tablet composite particles and 1% by weight of magnesium stearate, and a tablet with a total weight of 200 mg is produced using a single-punch tableting machine at a compression pressure of 150 MPa at 8 mm flat plate. did.
  • erythritol excipients as other tablet components
  • magnesium stearate lubricant
  • 10% by weight of silica / erythritol mixture and 1% by weight of magnesium stearate are mixed with erythritol, and the total weight is obtained using a single tableting machine under a tabletting pressure of 150 MPa in an 8 mm flat plate. 200 mg tablets were produced.
  • Example 3 The tablet hardness of the tablets produced in Example 3 and the tablets produced in Comparative Examples 3 and 4 were measured. Tablet hardness was measured using a portable checker (Okada Seiko Co., Ltd.). The measurement results are shown in Table 1. The tablet produced in Example 3 was significantly improved in tablet hardness as compared with the tablet produced in Comparative Example 3. Moreover, it was confirmed that the tablet manufactured in Example 3 has substantially the same tablet hardness as the tablet manufactured in Comparative Example 4.
  • silica porous silica powder (trade name: Silicia 350, Fuji Silysia Ltd.) was used. Moreover, erythritol (commercially available product) was used as a drug to be kneaded with silica or an excipient other than silica. The porous silica powder and erythritol are kneaded at a weight ratio of 1: 2, using a twin-screw kneader (trade name: KRC Jr., Kurimoto Seiko) at a temperature of 120 ° C. near the melting point of erythritol. It was. Thereby, composite particles for tablets were obtained.
  • a twin-screw kneader trade name: KRC Jr., Kurimoto Seiko
  • the composite particles for tablets and other tablet components were mixed and tableted to produce tablets.
  • erythritol excipient as another tablet component
  • crospovidone disintegrant
  • magnesium stearate lubricant
  • 10% by weight of composite particles for tablets, 10% by weight of crospovidone, and 1% by weight of magnesium stearate are mixed with erythritol.
  • a tablet (orally disintegrating tablet) having a total weight of 200 mg was produced using a tablet machine.
  • erythritol excipients as other tablet components
  • crospovidone disintegrant
  • magnesium stearate lubricant
  • Erythritol is mixed with 10% by weight of silica / erythritol composite particles, 10% by weight of crospovidone and 1% by weight of magnesium stearate, using a single-punch tableting machine at a compression pressure of 150 MPa at 8 mm flat plate.
  • a tablet (orally disintegrating tablet) having a total weight of 200 mg was produced.
  • Example 4 For the orally disintegrating tablet produced in Example 4 and the orally disintegrating tablet produced in Comparative Example 5, the tablet hardness and the disintegration time in the oral cavity were measured. Tablet hardness was measured using a portable checker (Okada Seiko Co., Ltd.). In addition, the disintegration time in the mouth is the start time when the measurer takes an orally disintegrating tablet with the cooperation of four measurers (healthy adult men and women of the age of 20-30). The swallowing of the taken orally disintegrating tablet was considered to have been disintegrated when the measurer raised his hand, and the time from the start time to the time when the measurer raised his hand was taken. The measurement results are shown in Table 2. The orally disintegrating tablet produced in Example 4 showed almost the same tablet hardness and disintegration time as the orally disintegrating tablet produced in Comparative Example 5.
  • the production method of the present invention can be preferably used for production of a tablet containing a poorly water-soluble drug as an active ingredient.
  • the production method of the present invention is less dependent on the type of drug, it can be used to provide a new tablet formulation to a pharmaceutical manufacturer who is a customer in the field of contracted drug manufacturing.

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Abstract

L'invention porte sur un procédé pour fabriquer de manière aisée un comprimé qui contient de la silice produite à bas coût. L'invention porte également sur : un comprimé contenant de la silice obtenu par le procédé; et des particules composites pour produire le comprimé. Le procédé de fabrication d'un comprimé contenant de la silice inclut une étape dans laquelle de la silice est malaxée conjointement avec un produit chimique fondu ou avec un excipient autre que la silice et le mélange résultant est ramené à la température ordinaire, permettant ainsi d'obtenir des particules composites pour des comprimés.
PCT/JP2009/057792 2008-04-17 2009-04-17 Procédé de fabrication d'un comprimé contenant de la silice, comprimé et particule composite pour le comprimé WO2009128543A1 (fr)

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JP2010508265A JPWO2009128543A1 (ja) 2008-04-17 2009-04-17 シリカを含む錠剤の製造方法、錠剤及び錠剤用複合粒子

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JP2008-107718 2008-04-17
JP2008107718 2008-04-17

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021063150A (ja) * 2019-10-10 2021-04-22 明彦 浪岡 凍結防止剤の製造方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6399012A (ja) * 1986-01-21 1988-04-30 Chugai Pharmaceut Co Ltd チオ−ルエステル誘導体の安定な固形剤
JPH07267850A (ja) * 1994-03-28 1995-10-17 Eisai Co Ltd 不快味を防止した医薬組成物及びその製造方法
WO2007034135A1 (fr) * 2005-09-22 2007-03-29 Reckitt Benckiser Healthcare (Uk) Limited Composition comprenant un ains et du paracetamol
JP2008509206A (ja) * 2004-08-12 2008-03-27 レキット ベンキーザー ヘルスケア （ユーケイ） リミテッド 溶融押出しにより作製するｎｓａｉｄ及び糖アルコールを含む顆粒

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6399012A (ja) * 1986-01-21 1988-04-30 Chugai Pharmaceut Co Ltd チオ−ルエステル誘導体の安定な固形剤
JPH07267850A (ja) * 1994-03-28 1995-10-17 Eisai Co Ltd 不快味を防止した医薬組成物及びその製造方法
JP2008509206A (ja) * 2004-08-12 2008-03-27 レキット ベンキーザー ヘルスケア （ユーケイ） リミテッド 溶融押出しにより作製するｎｓａｉｄ及び糖アルコールを含む顆粒
WO2007034135A1 (fr) * 2005-09-22 2007-03-29 Reckitt Benckiser Healthcare (Uk) Limited Composition comprenant un ains et du paracetamol

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021063150A (ja) * 2019-10-10 2021-04-22 明彦 浪岡 凍結防止剤の製造方法

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