# US 11,433,054 B2 · Pharmaceutical preparation and preparation method therefor

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- Number: US 11,433,054 B2
- Document ID: US11433054B2
- Status: Granted
- Kind: B2
- Application number: 16/626,084
- Filed: 2018-07-13
- Published: 2020-07-02
- Granted: 2022-09-06
- Earliest claimed: 2017-07-14
- Assignees: Daewoong Pharmaceutical Co., Ltd.
- Applicants: Daewoong Pharmaceutical Co., Ltd.
- Inventors: Jae Hee Yoon; Han Kang
- Web page: https://patentgrep.com/patent/US11433054B2

## CPC

- A61K 9/2853: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)}
- A61K 31/426: 1,3-Thiazoles
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2095: {Tabletting processes}
- A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2893: {Tablet coating processes (mechanical aspects A61J3/06)}
- A61K 9/5089: {Processes}
- A61K 47/02: Inorganic compounds
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/38: Cellulose; Derivatives thereof
- 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)

## Abstract

The present invention relates to a pharmaceutical preparation containing an active ingredient and a release-controlling agent for adjusting the release of the active ingredient, in which the active ingredient is at least one selected from among mirabegron and a pharmaceutically acceptable salt thereof, and the release-controlling agent is a hydrogel-forming polymer, the hydrogel-forming polymer being at least one selected from among polyethylene oxide, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, and hydroxyethyl cellulose and having an average molecular weight ranging from 100,000 to 8,000,000. The present invention is capable of suppressing the generation of impurities therein and of effectively controlling the release of at least one selected from among mirabegron and a pharmaceutically acceptable salt thereof.

## Claims

### Claim 1

A pharmaceutical preparation, comprising:
an active ingredient and a release-controlling agent for controlling release of the active ingredient, and further comprising:
a binder, an antioxidant, a lubricant, and a coating layer,
wherein the active ingredient is at least one selected from among mirabegron and a pharmaceutically acceptable salt thereof,
the release-controlling agent consists of a hydrogel-forming polymer,
the hydrogel-forming polymer is at least one selected from among polyethylene oxide, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, and hydroxyethyl cellulose, and has an average molecular weight ranging from 100,000 to 8,000,000,
the binder is at least one selected from among hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, methyl cellulose, carboxymethyl cellulose, sodium carboxymethylcellulose, trehalose, and pullulan,
the antioxidant is at least one selected from among butylhydroxytoluene, propyl gallate, butylhydroxyanisole, ascorbic acid, sodium ascorbate, erythorbic acid, sodium nitrite, sodium bisulfate, sodium pyrosulfite, citric acid and sodium edetate,
the lubricant is at least one selected from among magnesium stearate, calcium stearate, silicon dioxide, and talc,
the coating layer comprises a film of a coating agent dissolved or dispersed in ethanol and the coating layer is formed on a surface of a core prepared from the active ingredient, the release-controlling agent, the binder, the antioxidant, and the lubricant, and
the active ingredient is contained in an amount of 5 to 25 wt %, the release-controlling agent is contained in an amount of 60 to 90 wt %, the binder is contained in an amount of 1 to 5 wt %, the antioxidant is contained in an amount of 0.1 to 1 wt %, the lubricant is contained in an amount of 1 to 6 wt %, and the coating agent is contained in an amount of 1 to 10 wt % based on the total weight of the pharmaceutical preparation, wherein an amount of impurities is 0.2 wt % or less.

### Claim 2 (depends on 1)

The pharmaceutical preparation of claim 1, wherein the lubricant comprises silicon dioxide and magnesium stearate, and an amount of the silicon dioxide is 1 to 3 wt % and an amount of the magnesium stearate is 1 to 3 wt % in the pharmaceutical preparation.

### Claim 3 (depends on 2)

The pharmaceutical preparation of claim 2, wherein the silicon dioxide is colloidal silicon dioxide.

### Claim 4 (depends on 1)

The pharmaceutical preparation of claim 1, wherein the coating agent is a film-coating agent.

### Claim 5 (depends on 1)

The pharmaceutical preparation of claim 1, wherein the hydrogel forming polymer is polyethylene oxide, and the polyethylene oxide comprises polyethylene oxide having an average molecular weight ranging from 100,000 to less than 500,000 and polyethylene oxide having an average molecular weight ranging from 500,000 to less than 1,000,000.

### Claim 6 (depends on 1)

The pharmaceutical preparation of claim 1, wherein the hydrogel-forming polymer is polyethylene oxide and has an average molecular weight ranging from 100,000 to less than 1,000,000.

### Claim 7

A method of manufacturing a pharmaceutical preparation, the method comprising:
(A) manufacturing a granule by dispersing or dissolving a binder and an antioxidant in a solvent to afford a solution, which is then mixed with a mixture of an active ingredient and a release-controlling agent;
(B) obtaining a tablet by adding the granule with a lubricant and performing tableting; and
(C) coating the tablet with a film by dissolving or dispersing a film-coating agent in ethanol,
wherein the binder is hydroxypropyl cellulose,
the antioxidant is butylhydroxytoluene,
the active ingredient is at least one selected from among mirabegron and a pharmaceutically acceptable salt thereof,
the release-controlling agent consists of a hydrogel-forming polymer,
the hydrogel-forming polymer being at least one selected from among polyethylene oxide, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, and hydroxyethyl cellulose, and having an average molecular weight ranging from 100,000 to 8,000,000,
the lubricant comprises silicon dioxide and magnesium stearate, and
the active ingredient is contained in an amount of 5 to 25 wt %, the release-controlling agent is contained in an amount of 60 to 90 wt %, the binder is contained in an amount of 1 to 5 wt %, the antioxidant is contained in an amount of 0.1 to 1 wt %, the lubricant is contained in an amount of 1 to 6 wt %, and the coating agent is contained in an amount of 1 to 10 wt % based on the total weight of the pharmaceutical preparation, wherein an amount of impurities is 0.2 wt % or less.