Acetaminophen preparation, and method for producing same
Inventors
Sakamoto, Hiroshi • KOMAI, Kunio • Sakakibara, Kenji • BANBA, Hirokazu • Fukuda, Kiyoshi
Assignees
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Publication Number
US-11458102-B2
Publication Date
2022-10-04
Expiration Date
Abstract
A preparation which contains acetaminophen at a high content, in particular, a miniaturized tablet (conventional tablets, sustained-release tablets, etc.) which have excellent dissolution properties, preferable hardness and high drug content uniformity and a manufacturing method thereof. Acetaminophen has a preset particle size and is used for manufacturing a preparation, the flowability of acetaminophen can be improved so that secondary agglomeration can be suppressed, manufacturing efficiency can be elevated and the cost for manufacturing is also reduced. Thus, an acetaminophen preparation having improved administrability, for example, a reduced size and a manufacturing method thereof are highly useful.
Core Innovation
The invention relates to a method for manufacturing a tablet comprising acetaminophen by a dry direct compression method. The method uses unpulverized acetaminophen having a particle size distribution characterized by d10 in a range of 5 μm to 150 μm and d90 in a range of 200 μm to 1800 μm as measured by a laser-diffraction method. Water is added to the unpulverized acetaminophen so that a water addition ratio is in a range of 0.5 to 3% by weight relative to 100% by weight of the tablet.
Additives are blended with the acetaminophen, including at least one additive selected from an excipient, a dispersant, and a disintegrating agent. The method further includes blending a lubricant and compacting a mixture from the lubricant-blending step to produce the tablet. A key aspect is that deagglomeration and sizing are carried out at least one time from the step of water addition to the step of blending additives, to step of producing the tablet.
The deagglomeration and sizing are carried out to disperse and adhere the at least one additive to the surfaces of acetaminophen particles, thereby addressing secondary agglomeration and supporting dry direct compression. The document links the approach to flowability and electrostatic charging behavior of the acetaminophen preparation, and explains deagglomeration/sizing as a way to suppress secondary agglomeration rather than relying on pulverization.
Claims Coverage
The independent claim is directed to a manufacturing method for an acetaminophen tablet by dry direct compression. The claim includes 4 main inventive feature areas: (1) particle-size-defined unpulverized acetaminophen with controlled water addition, (2) blending selected excipient/dispersant/disintegrating agent, (3) lubricant blending and compaction to form a tablet, and (4) deagglomeration and sizing performed from the water-addition through the compaction-related steps to disperse and adhere additives to particle surfaces.
Laser-diffraction-defined unpulverized acetaminophen with controlled water addition
Adding water to unpulverized acetaminophen having a particle size distribution in which d10 is in a range of 5 μm to 150 μm and d90 is in a range of 200 μm to 1800 μm as measured by a laser-diffraction method, wherein an addition ratio of the water is in a range of 0.5 to 3% by weight relative to 100% by weight of the tablet.
Blending selected excipient, dispersant, and disintegrating agent
Blending at least one additive selected from the group consisting of an excipient, dispersant, and disintegrating agent.
Lubricant blending and compacting to produce the tablet by dry direct compression
Blending a lubricant; and compacting a mixture from step (c) to produce a tablet.
Deagglomeration and sizing to disperse and adhere additives onto acetaminophen particle surfaces
Carrying out deagglomeration and sizing at least one time in step (a) to step (c) to disperse and adhere the at least one additive to the surfaces of acetaminophen particles.
Across the independent claim, the method is structured around using laser-diffraction-defined unpulverized acetaminophen with controlled water addition, blending excipient/dispersant/disintegrating agent and a lubricant, and performing deagglomeration and sizing from early mixing through the additive-blending stages so that the additives disperse and adhere to acetaminophen particle surfaces during dry direct compression.
Stated Advantages
Suppresses secondary agglomeration.
Improves flowability/electrostatic charging behavior of the acetaminophen preparation for dry direct compression.
Disperses and adheres the at least one additive to the surfaces of acetaminophen particles.
Documented Applications
Manufacturing acetaminophen tablets via dry direct compression, including examples directed to tablet compositions and performance meeting Japanese Pharmacopoeia (JP) dissolution criteria [dissolution via JP paddle method/HPLC described].
Producing miniaturized tablets and sustained-release tablets [explicitly referenced in the provided content summary].
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