# US 10,946,003 B2 · Formulation having improved pH-dependent drug-release characteristics, containing esomeprazole or pharmaceutically acceptable salt thereof

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- Number: US 10,946,003 B2
- Document ID: US10946003B2
- Status: Granted
- Kind: B2
- Application number: 16/319,161
- Filed: 2017-07-24
- Published: 2019-08-08
- Granted: 2021-03-16
- Earliest claimed: 2016-07-25
- Assignees: Hanmi Pharm. Co., Ltd.
- Applicants: Hanmi Pharm. Co., Ltd.
- Inventors: Taek Kwan Kwon; Kwang Young Lee; Ho Taek Im; Yong Il Kim; Jae Hyun Park; Jong Soo Woo
- Web page: https://patentgrep.com/patent/US10946003B2

## CPC

- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 9/0002: {Galenical forms characterised by the drug release technique; Application systems commanded by energy}
- 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 9/28: Dragees; Coated pills or tablets {, e.g. with film or compression coating (A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209)}
- A61K 9/2846: {Poly(meth)acrylates}
- A61K 9/2886: {having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer (of the type active core-drug layer-inactive layer A61K9/209)}
- A61K 9/50: Microcapsules {having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals (A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167)}
- A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/5073: {having two or more different coatings optionally including drug-containing subcoatings}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61K 9/2893: {Tablet coating processes (mechanical aspects A61J3/06)}
- 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

Disclosed is a pharmaceutical formulation containing esomeprazole or a pharmaceutically acceptable salt thereof. The pharmaceutical formulation, based on considerably improved pH-dependent drug release characteristics, starts to release the esomeprazole or a pharmaceutically acceptable salt thereof at a target delay time after oral administration, continues the release for a predetermined time, and finishes the release after a predetermined time, thereby providing excellent patient convenience and excellent therapeutic effects, as compared to conventional other formulations.

## Claims

### Claim 1

A pharmaceutical formulation comprising:
(a) a core containing esomeprazole or a pharmaceutically acceptable salt thereof as an active ingredient;
(b) an endothelial coated layer formed on the core; and
(c) a release-control coated layer formed on the endothelial coated layer,
wherein the endothelial coated layer comprises at least one selected from the group consisting of hydroxypropyl methyl cellulose (HPMC), polyvinyl pyrrolidone (PVP), low-substituted hydroxypropyl cellulose (HPC-L), starch and gelatin,
the release-control coated layer comprises a polymer in which a methacrylic acid copolymer S and a methacrylic acid copolymer L are mixed in a ratio of 1.5:1 to 3.5:1 (w/w) as release-control coating base materials, and
wherein the weight of the methacrylic acid copolymer S and the methacrylic acid copolymer L, as the release-control coating base material, is 15 to 40% (w/w), with respect to a weight of the pharmaceutical formulation,
wherein, in a release test using an artificial intestinal fluid having a pH of 6.7 to 6.9, a number of revolutions of 75 rpm and 37° C. in accordance with the USP paddle method, 5% or less of the esomeprazole or a pharmaceutically acceptable salt thereof is eluted at up to 2 hours, and at least 90% of the esomeprazole or a pharmaceutically acceptable salt thereof is eluted after 6 hours.

### Claim 2 (depends on 1)

The pharmaceutical formulation of claim 1, wherein a content ratio of at least one substance selected from the group consisting of hydroxypropyl methyl cellulose (HPMC), polyvinyl pyrrolidone (PVP), low-substituted hydroxypropyl cellulose (HPC-L), starch and gelatin present in the endothelial coated layer, with respect to the weight of the methacrylic acid copolymer S and the methacrylic acid copolymer L, as the release-control coating base materials, is 3.5 to 8.0 (w/w), and
a content of at least one substance selected from the group consisting of hydroxypropyl methyl cellulose (HPMC), polyvinyl pyrrolidone (PVP), low-substituted hydroxypropyl cellulose (HPC-L), starch and gelatin, contained in the endothelial coated layer, is 4.4 to 5.2% (w/w), with respect to the weight of the tablet pharmaceutical formulation.

### Claim 3 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the esomeprazole or a pharmaceutically acceptable salt thereof is an esomeprazole magnesium salt or an esomeprazole strontium salt.

### Claim 4 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the esomeprazole or a pharmaceutically acceptable salt thereof is an anhydride or hydrate.

### Claim 5 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the core containing esomeprazole or a pharmaceutically acceptable salt thereof further comprises at least one excipient selected from diluents, binders, disintegrants, lubricants, surfactants, antioxidants, preservatives and stabilizers.

### Claim 6 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the pharmaceutical formulation is selected from the group consisting of a pellet, a mini-tablet, a tablet, a mixture of a pellet and a mini-tablet, and a capsule.