WO2009133774A1 - Granulés sphériques et leur procédé de fabrication - Google Patents

Granulés sphériques et leur procédé de fabrication Download PDF

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Publication number
WO2009133774A1
WO2009133774A1 PCT/JP2009/057673 JP2009057673W WO2009133774A1 WO 2009133774 A1 WO2009133774 A1 WO 2009133774A1 JP 2009057673 W JP2009057673 W JP 2009057673W WO 2009133774 A1 WO2009133774 A1 WO 2009133774A1
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Prior art keywords
sugar
spherical
granule
spherical granules
core particles
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PCT/JP2009/057673
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English (en)
Japanese (ja)
Inventor
照美 高橋
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フロイント産業株式会社
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Publication of WO2009133774A1 publication Critical patent/WO2009133774A1/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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug

Definitions

  • the present invention relates to a spherical granule suitable as a base material for pharmaceuticals and the like and an efficient production method thereof.
  • Nonparell registered trademark
  • the spherical granule is used as a preparation having a surface coated with various physiologically active substances, or a preparation having a functional coating layer formed on the surface thereof, or a preparation encapsulated in a capsule.
  • this spherical granule is used as a core particle to form a bioactive substance coating or a functional coating layer, the spherical granule may be damaged during the process if it is brittle.
  • a spherical granule having a strength capable of withstanding the processing in the apparatus in each process is required.
  • the shape of the spherical granule is true from the viewpoint of controlling the release of the physiologically active substance, for example, the release time as accurately as possible. It is required to be closer to a sphere and have a sharp particle size distribution.
  • a centrifugal fluid granulating device As a method for producing the spherical granule, a centrifugal fluid granulating device, an onion type pan coating device, or the like is used, and a liquid or powder containing sugar in particles serving as the core of the spherical granule (hereinafter referred to as “nuclear particle”).
  • a method of producing by granulating while supplying is known.
  • the obtained granule has a low sphericity and a spherical granule suitable for a preparation with controlled release of the physiologically active substance cannot be obtained. .
  • the spherical granules are granulated with a centrifugal fluidizing granulator, it is possible to produce granules having a higher sphericity than those granulated with an onion type pan coating apparatus. More specifically, granulated sugar crystals are charged as the core particles in the centrifugal flow granulator, and the sucrose fine particles or fine powder are dispersed while spraying an aqueous solution of sucrose as a binder on the surface of the core particles.
  • a method of forming spherical granules by forming a coating layer of the sucrose on the granulated sugar crystals see paragraph [0004] of Patent Document 1).
  • spherical granules with high sphericity can be obtained.
  • the present invention improves the friability and granule hardness to a sufficiently high level, has a high sphericity, and is coated with a physiologically active substance that can be taken orally on its surface and applied to the formulation. It is an object of the present invention to provide a high-quality spherical granule excellent in the release controllability of a physiologically active substance, and a method capable of efficiently and easily producing the spherical granule.
  • a coating layer is formed by spraying a liquid containing solids on the core particles without spraying the powder component while rolling by rotating a rotating dish in which the core particles containing sugar are horizontally installed.
  • a process for producing spherical granules comprising the step of forming In the method for producing spherical particles, since the core particles are rolled and granulated, the obtained spherical granules have a high sphericity. Further, at the time of granulation, the liquid is sprayed on the surface of the core particles while rolling, and a coating layer made of sugar or the like dissolved or dispersed in the liquid is formed on the surface of the core particles.
  • the spherical granules thus obtained have a high sphericity, excellent friability and granule hardness.
  • ⁇ 2> The method for producing a spherical granule according to ⁇ 1>, wherein the liquid containing solid content is an aqueous solution or suspension containing sugar.
  • ⁇ 3> The method for producing a spherical granule according to any one of ⁇ 1> to ⁇ 2>, wherein the core particles are sugar crystals or spray-dried particles of sugar and starch or a derivative thereof.
  • ⁇ 4> The nuclear particles according to any one of ⁇ 1> to ⁇ 3>, wherein the core particles are floated and flowed by blowing air into the rolling particles in addition to rolling by rotating a horizontally disposed rotating dish.
  • ⁇ 5> The spherical shape according to any one of ⁇ 1> to ⁇ 4>, further comprising spraying an aqueous solution of sugar and / or sugar alcohol on the surface of the obtained spherical granule to form a surface coating layer. It is a manufacturing method of a granule.
  • ⁇ 6> The method for producing a spherical granule according to any one of ⁇ 1> to ⁇ 5>, wherein the obtained spherical granule has a particle size of 75 to 1,000 ⁇ m as measured by a sieving method. . ⁇ 7> A spherical granule produced by the method for producing a spherical granule according to any one of ⁇ 1> to ⁇ 6>. ⁇ 8> A method for producing a preparation obtained by coating the surface of the spherical granule according to ⁇ 7> with a component containing a physiologically active substance that can be taken orally.
  • the above-mentioned problems in the prior art can be solved, and the friability and granule hardness are improved to a sufficiently high level. It is possible to provide a high-quality spherical granule excellent in the release controllability of a physiologically active substance, and a method capable of efficiently and easily producing the spherical granule.
  • the method for producing a spherical granule of the present invention includes at least a granulation step in which a spherical granule is granulated by rotating by rotating a rotating dish in which the core particles are horizontally installed and spraying a liquid on the core particles.
  • a granulation step in which a spherical granule is granulated by rotating by rotating a rotating dish in which the core particles are horizontally installed and spraying a liquid on the core particles.
  • other processes appropriately selected as necessary are included.
  • the spherical granules of the present invention are produced by the method for producing spherical granules of the present invention.
  • the granulation step rolls by rotating a rotating dish in which the core particles are horizontally installed, and sprays a liquid containing solids on the core particles without spraying powder components on the core particles.
  • spherical granules are formed by forming a coating layer.
  • the core particle can be appropriately selected according to the use and purpose of the spherical granule, and can be appropriately selected from known ones. In the present invention, it only needs to contain at least a sugar. In addition to sugar, other components may be contained.
  • a commercially available crystal grain or granulated product may be used as it is, or the crystal grain may be used after being polished, pulverized, or obtained by granulating a powder or the like. May be used.
  • the particle size of the core particle is not particularly limited and can be appropriately selected depending on the use and purpose of the spherical granule.
  • the particle size measured by a sieving method is preferably 50 to 850 ⁇ m. 75 to 500 ⁇ m is more preferable.
  • the particle size of the core particles exceeds 850 ⁇ m, the spherical particles obtained have a particle size of about 1,000 ⁇ m or more. Is likely to occur.
  • it is less than 50 ⁇ m aggregation may easily occur when spherical granules are formed or when a coating layer is formed on the surface of the obtained spherical granules.
  • sugar there is no restriction
  • the other components are not particularly limited as long as they can be taken orally, and can be appropriately selected according to the purpose. Examples thereof include sugar alcohols, organic acids and salts thereof, inorganic substances, starches and derivatives thereof, celluloses and the like.
  • Examples thereof include cellulose derivatives and synthetic polymers.
  • physiologically active substances are not used as other components. These may be used individually by 1 type and may use 2 or more types together. There are no particular restrictions on how to use them, and examples thereof include a method of granulating together with the above-mentioned sugar and coating the component on sugar crystal grains.
  • the sugar alcohol include mannitol, xylitol, erythritol, and the like.
  • Examples of the organic acid include citric acid, tartaric acid, ascorbic acid, and the like.
  • the salt of the organic acid include sodium salt, calcium salt, potassium salt and the like.
  • As said inorganic substance, salt, a titanium oxide, silicon dioxide etc. are mentioned, for example.
  • starch and derivatives thereof include corn starch, wheat starch, rice starch, and derivatives thereof.
  • cellulose and cellulose derivative include crystalline cellulose, powdered cellulose, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose acetate succinate, and the like.
  • synthetic polymer include polyvinyl pyrrolidone, poly (meth) acrylic acid and esters thereof, polyvinyl alcohol and derivatives thereof.
  • the liquid containing the solid content can be appropriately selected according to the use and purpose of the spherical granule, and can be appropriately selected from known ones.
  • the aqueous solution containing sugar Or suspension There is no restriction
  • this sugar 1 type may be used individually and 2 or more types may be used together. Depending on the kind of the sugar, since it has a binder effect, when the coating layer is formed on the surface of the core particle, the adhesive strength between the coating layer and the core particle is excellent.
  • the content of the sugar in the liquid containing the solid content is not particularly limited, and may be adjusted to a concentration according to the solubility of the sugar.
  • a concentration according to the solubility of the sugar For example, in the case of sucrose, 20 to 60% by weight is preferable. If the sugar content is less than 20% by weight, it is assumed that the production efficiency is lowered due to the extension of the process time for spraying the liquid, and if it exceeds 60% by weight, aggregation occurs due to the binder effect of sucrose. There is. Moreover, it is preferable that the whole amount of sugar is dissolved in the liquid.
  • the additive component other than the sugar contained in the liquid containing the solid content is not particularly limited as long as it can be taken orally, sugar alcohol, organic acid and salt thereof, inorganic substance, starch and derivative thereof, cellulose.
  • examples thereof include derivatives and synthetic polymers.
  • examples of the sugar alcohol, the organic acid and salt thereof, the starch and derivative thereof, the cellulose and cellulose derivative, and the synthetic polymer include those described above.
  • the physiologically active substance is not contained as a solid content.
  • the content of the dispersoid is preferably 30% by weight or less, and more preferably 20% by weight or less. If the content of the additive component exceeds 30% by weight, the viscosity may be high, depending on the properties of the component to be added, and sprayability may be deteriorated or aggregation may easily occur.
  • the solvent contained in the liquid include water. There is no restriction
  • the organic solvent etc. may be contained in the range which does not injure the objective of this invention other than water.
  • the organic solvent alcohol, such as ethanol, etc. are mentioned suitably, for example. If the liquid contains the organic solvent, the solubility may be improved and the drying time may be shortened.
  • the solubility may be improved and the drying time may be shortened.
  • the objective it can select suitably.
  • the method for preparing the liquid containing the solid content is not particularly limited, and can be prepared according to a known method according to the purpose.
  • the sugar, additional components other than the sugar are added to water, or as necessary.
  • the method for spraying the liquid containing the solid content onto the core particles is not particularly limited and can be appropriately selected depending on the purpose.
  • spray means provided in the granulating apparatus to be used for example, A method of spraying from a spray gun, a spray nozzle or the like is preferable.
  • the spraying conditions are not particularly limited, and publicly known conditions can be adopted.
  • the spraying amount, the size of sprayed mist particles (mist), the spraying time, and the like are determined according to the purpose. It can be selected appropriately.
  • the spray air pressure is preferably about 0.1 MPa to 0.5 MPa, for example.
  • the granulator is not particularly limited as long as it can roll the core particles in the present invention, and can be appropriately selected from known ones according to the purpose.
  • Centrifugal flow type coating granulator for example, “CF Granulator” manufactured by Freund Sangyo Co., Ltd.
  • composite type granulating coating device for example, “Spiraflow” manufactured by Freund Sangyo Co., Ltd.
  • centrifugal rolling granulation coating A device for example, “Granurex” manufactured by Freund Sangyo Co., Ltd.
  • Gnurex manufactured by Freund Sangyo Co., Ltd.
  • the powder such as sugar is sprayed from a powder spraying device to the core particles during the spraying.
  • the friability and granule hardness could not be sufficiently improved.
  • the friability and granule hardness were sufficiently high. In order to obtain high-quality spherical granules with improved levels, the powder is not applied to the core particles during the application.
  • the rolling is also referred to as “centrifugal flow” or “centrifugal rolling”, and a rotating plate (rotor) installed horizontally inside a cylindrical fixed wall (stator) rotates, It means that the core particles roll on the rotor while introducing slit air supplied from a constant clearance provided between the rotors.
  • the core particles are formed into a spherical shape while a coating layer made of the liquid containing the solid content is formed on the surface thereof.
  • the method of using the well-known granulator provided with the rotor and stator which can rotate etc. is mentioned suitably.
  • the granulator is not particularly limited and may be appropriately selected depending on the intended purpose.
  • examples thereof include a centrifugal flow type coating granulator (for example, “CF Granulator” manufactured by Freund Sangyo Co., Ltd.), a composite Preferred examples include a mold granulation coating apparatus (for example, “Spiraflow” manufactured by Freund Sangyo Co., Ltd.), a centrifugal rolling granulation coating apparatus (for example, “Granurex” manufactured by Freund Sangyo Co., Ltd.), and the like.
  • the rolling condition is not particularly limited and may be appropriately selected depending on the purpose. However, the rotational speed of the rotor may vary depending on the apparatus diameter, but may vary depending on the device diameter, but may be about 50 to 1,000 rpm. Is preferred.
  • the temperature at the time of rolling is not particularly limited and may be appropriately selected depending on the kind of the core particles, the composition of the liquid, and the like, but the product temperature is preferably about 20 to 50 ° C.
  • a screen that does not allow the passage of nuclear particles but allows air to pass through is provided on the rotating dish, and floating air is introduced by blowing air toward the rolling particles from below the rotating dish, or near the rotating dish from above the rotating dish.
  • Floating fluid air can be introduced toward the rolling particles by the provided tubular air supply means.
  • the air volume of the slit air and the floating fluid air can be appropriately selected according to the purpose such as the capacity of the apparatus.
  • the rolling floating flow method is not particularly limited, and a method using a known granulator equipped with a rotatable rotor and slit air and a floating flow air path is preferable.
  • the granulator is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a composite granulation coating apparatus (for example, “Spiraflow” manufactured by Freund Sangyo Co., Ltd.), centrifugal rolling, etc.
  • a granulating and coating apparatus for example, “Granurex” manufactured by Freund Sangyo Co., Ltd.) and the like are preferable.
  • a coating layer made of the liquid containing the solid content is formed on the surface of the core particles, and the spherical granules of the present invention are granulated.
  • the coating amount of the coating layer is not particularly limited and can be appropriately selected according to the use and purpose of the spherical granule.
  • the sugar contained in the liquid with respect to the core particles The solid content is preferably about 50 to 1,500% by weight, more preferably about 100 to 1,000% by weight.
  • the particle size of the spherical granule is not particularly limited and can be appropriately selected depending on the use and purpose of the spherical granule.
  • the particle size measured by a sieving method is 75 to 1,000 ⁇ m. It is preferably 150 to 850 ⁇ m.
  • the particle diameter of the spherical granule exceeds 1,000 ⁇ m, there are cases where problems such as a poor feeling of taking of the preparation are likely to occur when formulated using the obtained spherical granule, whereas the particle diameter is less than 75 ⁇ m. When it exists, it may become easy to raise
  • the sphericity of the spherical granules thus obtained is preferably 0.85 or more, more preferably 0.90 or more.
  • the solubility of the physiologically active substance in the preparation in the body is not uniform, and the drug delivery Quality as a system-applied formulation may be insufficient.
  • it is 0.85 or more when a coating layer containing a physiologically active substance or the like is formed on the surface of the spherical granule, the physiologically active substance can be uniformly coated and the release of the physiologically active substance This is advantageous in that the speed can be controlled more accurately.
  • the spherical granules have high sphericity because they are granulated by rolling the core particles.
  • the liquid is sprayed and components such as sugar dissolved or dispersed in the liquid form a coating layer on the surface of the core particles, so that the spherical granules have a friability.
  • the surface coating layer forming step is a step of forming a surface coating layer on the surface of the spherical granule obtained in the granulation step.
  • the spherical granule of the present invention may be one in which the surface coating layer is not formed, or one in which the surface coating layer is formed.
  • the spherical granules having the surface coating layer are improved in their friability, granule hardness, and the like as compared with the case where the surface coating layer is not formed.
  • the method for forming the surface coating layer is not particularly limited and can be appropriately selected according to the purpose.
  • the method etc. which are performed by spraying a surface coating layer forming liquid are mentioned.
  • limiting in particular as said surface coating layer forming liquid although it can select suitably according to the objective, The thing similar to the liquid containing the said solid content mentioned above is mentioned suitably.
  • the liquid may be either an aqueous solution or a suspension.
  • the surface coating layer forming liquid may be used in terms of the degree of friability of the resulting spherical granules, improvement in granule hardness, and the like. From an aqueous solution is preferred over a suspension. In the present invention, an aqueous solution of the sugar and / or sugar alcohol is particularly preferable.
  • the coating amount of the surface coating layer is not particularly limited and can be appropriately selected depending on the use and purpose of the spherical granule. For example, it is contained in the surface coating layer forming liquid for the core particles.
  • the ratio of the solids such as sugar is preferably about 1 to 200% by weight, more preferably about 10 to 100% by weight.
  • the centrifugal rolling granulation coating apparatus “Granurex” (manufactured by Freund Sangyo Co., Ltd.) includes a granulation chamber capable of granulating spherical granules while rolling the core particles.
  • the granulation chamber has a space having a circular cross section on the installation surface, and a circular rotating plate (rotor) in which the plate surface is installed horizontally with respect to the installation surface in the space. ).
  • the rotor has a shape in which the outer peripheral edge portion is gradually inclined upward. When the rotor is rotated around the rotation axis, the core particles can roll on the dish surface.
  • a predetermined clearance is formed between the outer peripheral end of the rotor and the inner wall of the granulation chamber.
  • the granulation chamber is provided with a thermometer such as a thermocouple for measuring the temperature in the space.
  • the granulation chamber is also provided with a spraying device so that the liquid for forming the coating layer on the surface of the core particles can be sprayed into the granulation chamber.
  • the spraying device is provided above the rotor and in the vicinity of the outer peripheral edge thereof, and a pipe and a pump for feeding the liquid, and the liquid can be sprayed into the space.
  • a spray nozzle is provided in the granulation chamber, an air chamber is formed below the rotor, and air can be pumped into the air chamber, and the inside of the granulation chamber (inside the space) from the clearance portion. ) Slit air can be introduced.
  • the core particles when the core particles are introduced while the rotor is rotated and slit air is introduced, the core particles roll. Next, when the liquid containing the solid content for forming the coating layer is sprayed, the surface of the core particles is coated with the components such as the sugar contained in the liquid containing the solid content to form spherical granules. .
  • the spherical granules obtained in this way can be taken out from the centrifugal rolling coating device and transferred to a fluidized bed device or the like, and further subjected to a drying process, etc.
  • the particles In the granulation chamber, the particles can be rolled and floated by feeding air into the rolling particles. Therefore, since this floating fluidized air is introduced during granulation, the drying efficiency is improved, so that granulation can be performed more efficiently.
  • the spherical granule obtained by the method for producing a spherical granule of the present invention is the spherical granule of the present invention, and the spherical granule can be suitably used as a spherical granule for preparation. Since the spherical granule has improved friability and granule hardness, the spherical granule is coated with the physiologically active substance on the surface thereof to produce a defective product due to damage of the spherical granule. The rate is also low.
  • the physiologically active substance when the surface is coated with the physiologically active substance or the like to form a preparation, the physiologically active substance can be uniformly dissolved in the body and is suitable for a drug delivery system or the like. It can be a high quality formulation.
  • a preparation using the spherical granule of the present invention there is no particular limitation on the method of preparing a preparation by forming a coating layer containing a physiologically active substance on the surface of the spherical granule.
  • a powder containing a physiologically active substance is supplied while spraying a binding solution to perform coating. It can be carried out under known conditions such as powder coating granulation, spray coating method in which a solution in which a physiologically active substance or binder is dissolved or suspended is sprayed to coat.
  • the component constituting the bioactive substance-containing coating layer is not particularly limited and can be appropriately selected according to the purpose.
  • a pharmaceutical additive or a food additive is used. Also good. These may be used individually by 1 type and may use 2 or more types together.
  • the physiologically active substance is not particularly limited as long as it can be taken orally, and can be appropriately selected according to the purpose.
  • hypnosis / sedation antipyretic analgesic / antiinflammatory agent, neuropsychiatric agent, autonomic nerve Preparations, antiparkinsonian agents, antihistamines, cardiotonic agents, diuretics, antihypertensive agents, vasoconstrictors, arteriosclerotic agents, antitussive expectorants, vitamins, nourishing tonics, antibiotics, gastrointestinals, and the like.
  • the pharmaceutical additive and the food additive are not particularly limited as long as they can be taken orally, and can be appropriately selected according to the purpose.
  • a functional coating layer may be formed in addition to the physiologically active substance-containing coating layer.
  • the functional coating layer is a layer formed for the purpose of controlling the release rate of the physiologically active substance such as sustained release, gastric solubility, entericity, etc., or for the purpose of moisture proofing, light shielding, bitterness and odor masking.
  • the functional coating layer may be formed under known conditions depending on the purpose of the preparation.
  • the component for forming the functional coating layer is not particularly limited as long as it can be taken orally, and examples thereof include natural polymers and synthetic polymers. As described above, various preparations can be obtained.
  • the obtained spherical granule has a minor axis and a major axis, and is a value represented by a ratio of the minor axis / major axis.
  • the ratio of the minor axis / major axis means the ratio between the minor axis and the major axis of the spherical granule, and is a standard indicating the sphericity.
  • the ratio of the minor axis to the major axis is determined by randomly placing the obtained spherical granules on a sample stage, taking a photograph, and measuring the length of the major axis (major axis) of the 50 spherical granules at the midpoint of the major axis.
  • the lengths of the minor axes perpendicular to each other (minor axis) are measured, the ratio of the minor axis to the major axis is determined for each, and the average value of 50 is shown.
  • the evaluation criteria for sphericity are as follows. ⁇ ⁇ ⁇ ⁇ Sphericality 0.90 or more ⁇ ⁇ ⁇ Sphericality 0.85 or more and less than 0.90 ⁇ ⁇ ⁇ ⁇ Sphericality less than 0.85
  • Friction degree (%) (Wt ⁇ Ws) / Wt ⁇ 100 (i)
  • Friction degree (%) (Wt ⁇ Ws) / Wt ⁇ 100 (i)
  • Example 1 Using a composite granulation coating apparatus (Freund Sangyo Co., Ltd., “Spiraflow”, SFC-5), suspensions of the formulations shown in Table 2 below are prepared as core particles (particle size is 150 to 212 ⁇ m).
  • the weight of the sucrose and corn starch in the suspension is 700% by weight with respect to the weight of the granulated sugar crystals (sucrose crystals, manufactured by Shisui Minato Seika Co., Ltd.).
  • Spherical granules were granulated by covering the surface of core particles (granulated sugar crystals).
  • the operating conditions of the composite granulation coating apparatus include a total air volume (floating air flow amount + slit air amount) of 3.4 m 3 / min (80 ° C. setting), a rotor rotational speed of 300 rpm, and a spray air pressure.
  • a total air volume floating air flow amount + slit air amount
  • a rotor rotational speed 300 rpm
  • a spray air pressure 300 rpm
  • the composite granulation coating apparatus includes the granulation chamber described above, and a rotatable rotor is provided in the granulation chamber. Further, the inner wall of the granulation chamber is provided with a spraying device (spray gun) capable of spraying the suspension toward the core particles near and above the outer peripheral edge of the rotor. Yes. In addition, a slight clearance is provided between the outer peripheral edge of the rotor and the inner wall of the granulation chamber, so that slit air can pass through the clearance from below and be introduced into the granulation chamber. Yes. Further, a part of the rotor is a screen that allows ventilation, and floating fluid air can be introduced from this screen portion.
  • a spraying device spray gun
  • the core particles when the core particles are introduced while the rotor is rotated and the slit air is introduced into the granulation chamber, the core particles cause the rolling.
  • the rolling floating flow is generated.
  • the resulting spherical granules have a sphericity of 0.87, a friability of 1.08%, a granule hardness of 169 g, and a yield of about 88 when screened with a particle size of 355 to 500 ⁇ m. %Met.
  • the sphericity, the friability, and the granule hardness were measured and evaluated by the methods described above.
  • the yield is a value calculated by a sieving method.
  • Example 2 After granulating the spherical granules under the same formulation and conditions as in Example 1, the solution of the formulation shown in Table 2 (the surface coating layer forming solution) was further added to the weight of the core particles with respect to the sucrose content in the solution. Spherical granules were granulated in the same manner as in Example 1 except that the surface of the spherical granules was coated (sprayed) to form a coating amount of 50% by weight in terms of solid content.
  • the resulting spherical granule has a sphericity of 0.88, a friability of 0.18%, a granule hardness of 190 g, and a yield of about 88 when screened with a particle size of 355 to 500 ⁇ m. %Met.
  • Example 3 Spherical granules were obtained in the same manner as in Example 1 except that the particle size of granulated sugar as the core particle was changed to 212 to 300 ⁇ m and the coating amount by coating was changed from 700% by weight to 900% by weight. The same evaluation as in Example 1 was performed.
  • the obtained spherical granule has a sphericity of 0.90, a friability of 1.33%, a granule hardness of 345 g, and a yield of about 96 when the particle size is 500 to 710 ⁇ m. %Met.
  • Example 4 In Example 3, after changing the composition of the suspension to the formulation shown in Table 2 and granulating spherical granules in the same manner as in Example 3, the solution having the formulation shown in Table 2 (the surface coating layer forming solution) Except that the surface coating layer is formed by coating (spraying) the surface of the spherical granules so that the coating amount is 50% by weight with respect to the weight of the core particles. Were granulated in the same manner as in Example 3. The resulting spherical granule has a sphericity of 0.90, a friability of 0.45%, a granule hardness of 360 g, and a yield of about 95 when screened with a particle size of 500-710 ⁇ m. %Met.
  • Example 5 In Example 4, a centrifugal tumbling granulation coating apparatus (manufactured by Freund Sangyo Co., Ltd., “Granurex”, GX-40) was used instead of the composite granulation coating apparatus, and the formulation shown in Table 2 Spherical granules were granulated in the same manner as in Example 4 except that the above suspension was used.
  • the operating conditions of the centrifugal rolling granulation coating apparatus are as follows: the total air volume (floating air flow amount + slit air amount) is 2.5 m 3 / min (80 ° C.
  • the obtained spherical granule has a sphericity of 0.91, a friability of 0.49%, a granule hardness of 341 g, and a yield of about 91 when screened with a particle size of 500 to 710 ⁇ m. %Met.
  • the operating conditions of the composite granulation coating apparatus include a total air volume (floating air flow amount + slit air amount) of 3.0 m 3 / min (70 ° C.
  • the spray rate of the liquid was adjusted so that the air pressure was 0.4 MPa and the exhaust temperature was around 43 ° C.
  • the resulting spherical granules have a sphericity of 0.98, a friability of 0.05%, a granule hardness of 42 g, and a yield of about 73 when sieved with a particle size of 150-250 ⁇ m. %Met.
  • the obtained granules were evaluated in the same manner as in Example 1.
  • the operating conditions of the centrifugal flow type coating granulator are as follows: the slit air amount is 0.18 m 3 / min, the rotor rotational speed is 160 rpm, the spray air pressure is 0.1 MPa, and the liquid speed is 5 to 10 mL / min. It was set to min.
  • the amount of the mixed powder applied was adjusted between 20 and 70 g / min.
  • the obtained spherical granules had a sphericity of 0.93, a friability of 1.49%, a granule hardness of 93 g, and a yield when sieved with a particle size of 355 to 500 ⁇ m.
  • the obtained granules were evaluated in the same manner as in Example 1.
  • the operating conditions of the centrifugal flow type coating granulator are as follows: the slit air amount is 0.18 m 3 / min, the rotor rotational speed is 160 rpm, the spray air pressure is 0.1 MPa, and the liquid speed is 5 to 10 mL / min. It was set to min.
  • the amount of the mixed powder applied was adjusted between 20 and 70 g / min.
  • the obtained spherical granule has a sphericity of 0.94, a friability of 1.85%, a granule hardness of 152 g, and a yield when sieved with a particle size of 500 to 710 ⁇ m.
  • the obtained spherical granules were evaluated in the same manner as in Example 1.
  • the operating conditions of the centrifugal flow type coating granulator are as follows: the slit air amount is 0.18 m 3 / min, the rotor rotational speed is 160 rpm, the spray air pressure is 0.1 MPa, and the liquid speed is 5 to 10 mL / min. It was set to min. The amount of the mixed powder applied was adjusted between 20 and 70 g / min.
  • the obtained spherical granule has a sphericity of 0.93, a friability of 0.36%, a granule hardness of 13 g, and a yield when sieved with a particle size of 150 to 250 ⁇ m. Was about 61%.
  • the spherical granule obtained in Example 6 having the same particle size with the spherical granule obtained in Comparative Example 3, the spherical granule obtained in Example 6 is more granular than the spherical granule of Comparative Example 3. An increase in hardness and a decrease in friability were confirmed.
  • the method for producing spherical granules of the present invention while using a method in which only the liquid is sprayed on the core particles composed of crystal grains, the sphericity granules are excellent in friability and granule hardness compared to spherical granules granulated by powder coating. Since a high-quality spherical granule with high sphericity is obtained, the method for producing a spherical granule of the present invention is suitable for producing a spherical granule suitable as a core particle for a preparation used for efficiently producing a high-quality preparation. Can be used.
  • the spherical granule of the present invention is more suitable as a core particle for pharmaceutical preparations used in controlled release preparations and the like because it is superior in friability, granule hardness, high sphericity and high quality than spherical granules granulated by powder coating. Can be used.

Abstract

L'invention porte sur des granulés sphériques qui ont été améliorés en ce qui concerne l'abrasivité et la dureté granulaire, à un niveau suffisamment élevé de chacune de ces propriétés, et qui présentent une sphéricité élevée et, dans le cas où ils sont revêtus en surface par une substance physiologiquement active ou similaire et employés dans une préparation médicinale, qui présentent une excellente aptitude à réguler la libération de la substance physiologiquement active, et sur un procédé par lequel les granulés sphériques décrits ci-dessus peuvent être produits de façon efficace et pratique. L'invention porte sur un procédé de production des granulés sphériques caractérisé par le fait qu'il comporte, tout en polissant au tambour des grains de noyau contenant du sucre par rotation d'une plaque rotative qui est située horizontalement, la pulvérisation d'un liquide contenant des matières solides sur les grains de noyau sans libération d'un composant pulvérulent. Dans des modes de réalisation préférés, le liquide décrit ci-dessus est une solution ou une suspension aqueuse contenant un sucre, les grains de noyau décrits ci-dessus contiennent des cristaux de sucre ou des grains séchés par pulvérisation d'un sucre, d’un amidon d'un dérivé de celui-ci, et une solution aqueuse contenant un sucre et/ou un alcool de sucre est en outre pulvérisée sur la surface des granulés sphériques obtenus ci-dessus pour ainsi former une couche de revêtement de surface. L'invention porte également sur des granulés sphériques caractérisés par le fait qu'ils sont produits par le procédé décrit ci-dessus de production de granulés sphériques.
PCT/JP2009/057673 2008-04-28 2009-04-16 Granulés sphériques et leur procédé de fabrication WO2009133774A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019060360A1 (fr) * 2017-09-22 2019-03-28 Honeywell International Inc. Procédé de granulation de poudres

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012066656A1 (fr) * 2010-11-17 2012-05-24 日本たばこ産業株式会社 Granulés à adsorbant supporté et leur procédé de fabrication, filtre à cigarette et cigarette
JP2021088507A (ja) * 2019-12-02 2021-06-10 ノーベルファーマ株式会社 シロリムス含有顆粒製剤、及びその製造方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09263589A (ja) * 1996-01-24 1997-10-07 Freunt Ind Co Ltd 乳糖の球形粒及びその製造方法
JPH1192403A (ja) * 1997-07-23 1999-04-06 Freunt Ind Co Ltd 単一物質球形粒、該球形粒を含む医薬、食品及びそれらの製造方法
WO2002036168A1 (fr) * 2000-11-06 2002-05-10 Asahi Kasei Kabushiki Kaisha Particules cellulosiques destinees a des preparations pharmaceutiques

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3349535B2 (ja) * 1993-01-12 2002-11-25 フロイント産業株式会社 球形顆粒の製造方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09263589A (ja) * 1996-01-24 1997-10-07 Freunt Ind Co Ltd 乳糖の球形粒及びその製造方法
JPH1192403A (ja) * 1997-07-23 1999-04-06 Freunt Ind Co Ltd 単一物質球形粒、該球形粒を含む医薬、食品及びそれらの製造方法
WO2002036168A1 (fr) * 2000-11-06 2002-05-10 Asahi Kasei Kabushiki Kaisha Particules cellulosiques destinees a des preparations pharmaceutiques

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019060360A1 (fr) * 2017-09-22 2019-03-28 Honeywell International Inc. Procédé de granulation de poudres

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