# US 11,433,031 B2 · Method for manufacturing acetaminophen preparation

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- Number: US 11,433,031 B2
- Document ID: US11433031B2
- Status: Granted
- Kind: B2
- Application number: 17/222,237
- Filed: 2021-04-05
- Published: 2021-07-22
- Granted: 2022-09-06
- Earliest claimed: 2016-05-10
- Assignees: Nippon Zoki Pharmaceutical Co., Ltd.
- Applicants: Nippon Zoki Pharmaceutical Co., Ltd.
- Inventors: Hiroshi Sakamoto; Kunio Komai; Kenji Sakakibara; Hirokazu Banba; Kiyoshi Fukuda
- Web page: https://patentgrep.com/patent/US11433031B2

## CPC

- A61K 9/2095: {Tabletting processes}
- A61K 9/20: Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets}
- A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
- A61K 47/02: Inorganic compounds
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/30: Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A method for manufacturing a preparation which contains acetaminophen at a high content, in particular, a miniaturized tablet (conventional tablets, sustained-release tablets, etc.) which have excellent elution properties, preferable hardness and high drug content uniformity, and a premix drug substance of acetaminophen which has improved manufacturability. According to the method in which acetaminophen having a preset particle size is used for manufacturing a preparation, the flowability of acetaminophen can be improved so that secondary agglomeration can be suppressed and manufacturing efficiency can be elevated. Thus, this method is highly useful for manufacturing an acetaminophen preparation having improved administrability, for example, a reduced size.

## Claims

### Claim 1

A method for manufacturing a premix drug substance, wherein the method includes the steps of blending a dispersant in an amount of 0.1 to 3% relative to 100% by weight of the premix drug substance and optionally a solubilizing agent in an amount of 0 to 0.8% by weight relative to 100% by weight of the premix drug substance into unpulverized acetaminophen having a particle size distribution that d10 is 5 to 300 μm, d50 is about 120 to about 500 μm, and d90 is 200 to 900 μm in an amount of 90 to 99.9% by weight relative to 100% by weight of the premix drug substance; and then carrying out deagglomeration and/or sizing to disperse and make adhere the dispersant, or the dispersant and the solubilizing agent in and onto the surfaces of the acetaminophen particles uniformly to make powder and wherein the process prevents deterioration of agglomeration and poor flowability, wherein the dispersant is at least one of hydrated silicon dioxide or light anhydrous silicic acid.

### Claim 2 (depends on 1)

The manufacturing method according to claim 1, wherein the acetaminophen has the particle size distribution that d10 is 10 to 200 μm and d90 is 250 to 800 μm.

### Claim 3 (depends on 1)

The manufacturing method according to claim 1, wherein the dispersant is hydrated silicon dioxide.

### Claim 4 (depends on 1)

The manufacturing method according to claim 1, wherein the solubilizing agent is macrogol or sodium lauryl sulfate.