# US 11,896,718 B2 · Core tablet composite preparation comprising mosapride and rabeprazole

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- Number: US 11,896,718 B2
- Document ID: US11896718B2
- Status: Granted
- Kind: B2
- Application number: 16/768,805
- Filed: 2018-11-26
- Published: 2021-06-17
- Granted: 2024-02-13
- Earliest claimed: 2017-12-14
- Applicants: Korea United Pharm. Inc.
- Inventors: Byung Jin Kim; Hee Yong Song; Youn Woong Choi; Seong Yeob Kim
- Web page: https://patentgrep.com/patent/US11896718B2

## CPC

- A61K 9/209: {containing drug in at least two layers or in the core and in at least one outer layer}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- 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 9/2072: {characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms (A61K9/0004, A61K9/0056, A61K9/0065 take precedence)}
- A61K 9/2095: {Tabletting processes}
- A61K 9/2806: {Coating materials}
- A61K 9/2846: {Poly(meth)acrylates}
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/535: having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K 31/5375: 1,4-Oxazines, e.g. morpholine
- 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 composite preparation in a core tablet form, composed of an inner core containing rabeprazole as an effective ingredient; an outer layer portion including the bilayer structure of a sustained release layer and an immediate release layer and containing mosapride as an effective ingredient. The core tablet composite preparation according to the present invention is characterized by exerting sufficient pharmacological activity of rabeprazole and mosapride even upon administration of one tablet once a day.

## Claims

### Claim 1

A mosapride- and rabeprazole-containing tablet-in-tablet combined preparation for oral administration, the tablet-in-tablet combined preparation composed of:
an inner core containing rabeprazole or a pharmaceutically acceptable salt thereof as an active ingredient; and
an outer layer part containing mosapride or a pharmaceutically acceptable salt thereof as an active ingredient,
wherein an entire surface of the inner core is surrounded by the outer layer part, and
the outer layer part has a bilayer structure of an immediate-release layer containing an active ingredient, a filler, a disintegrant, and an additive and a sustained-release layer containing an active ingredient, a filler, a disintegrant, a release-modifying agent, and an additive,
wherein the inner core is positioned more toward an immediate-release layer side of the outer layer part, and
wherein an area of the inner core surface surrounded by the immediate-release layer of the outer layer part is larger than an area of the inner core surface surrounded by the sustained-release layer of the outer layer part.

### Claim 2 (depends on 1)

The tablet-in-tablet combined preparation of claim 1, wherein a weight ratio of the sustained-release layer and the immediate-release layer of the outer layer part ranges from 1:1.5 to 1:2.5.

### Claim 3 (depends on 1)

The tablet-in-tablet combined preparation of claim 1, wherein, as the release-modifying agent, a mixture of hydroxypropyl methylcellulose having a viscosity of 75,000 to 140,000 mPa·s and hydroxypropyl methylcellulose having a viscosity of 3,000 to 5,600 mPa·s is used, and, with respect to a total weight of the release-modifying agent, 60 to 70 wt % of the hydroxypropyl methylcellulose having a viscosity of 75,000 to 140,000 mPa·s and 30 to 40 wt % of the hydroxypropyl methylcellulose having a viscosity of 3,000 to 5,600 mPa·s are included.

### Claim 4 (depends on 1)

The tablet-in-tablet combined preparation of claim 1, wherein the immediate-release layer of the outer layer part contains 4 to 6 mg of the active ingredient, and the sustained-release layer contains 9 to 12 mg of the active ingredient.

### Claim 5 (depends on 1)

The tablet-in-tablet combined preparation of claim 1, wherein the sustained-release layer of the outer layer part contains, with respect to a total weight of the sustained-release layer, 12 to 16 wt % of mosapride citrate and 20 to 40 wt % of the release-modifying agent.

### Claim 6 (depends on 1)

The tablet-in-tablet combined preparation of claim 1, wherein a total weight of the inner core ranges from 30 to 70 mg.

### Claim 7 (depends on 1)

The tablet-in-tablet combined preparation of claim 1, wherein the inner core is coated with an enteric coating agent, and a total weight of the inner core ranges from 40 to 60 mg.

### Claim 8 (depends on 1)

The tablet-in-tablet combined preparation of claim 1, wherein a total weight of the tablet-in-tablet combined preparation ranges from 250 to 350 mg.

### Claim 9

A method of preparing a mosapride- and rabeprazole-containing tablet-in-tablet combined preparation for oral administration, the method comprising:
preparing an inner core containing rabeprazole or a pharmaceutically acceptable salt thereof as an active ingredient;
preparing immediate-release layer granules containing mosapride or a pharmaceutically acceptable salt thereof as an active ingredient, a filler, a disintegrant, and an additive and sustained-release layer granules containing mosapride or a pharmaceutically acceptable salt thereof as an active ingredient, a filler, a disintegrant, a release-modifying agent, and an additive;
feeding the immediate-release layer granules into a punch die of a tablet press machine;
adding the inner core to the punch die into which the immediate-release layer granules have been fed;
applying pre-pressure to the punch die to which the inner core has been added;
feeding the sustained-release layer granules into the punch die to which pre-pressure has been applied; and
performing tableting while applying main pressure to the punch die into which the sustained-release layer granules have been fed such that a surface area of the inner core surrounded by the immediate-release layer granules is larger than a surface area of the inner core surrounded by the sustained-release layer granules,
wherein the inner core is positioned more toward the immediate-release layer granules of an outer layer part.

### Claim 10 (depends on 9)

The method of claim 9, wherein the pre-pressure ranges from 0.5 to 2 kgf/cm2, and the main pressure ranges from 3 to 20 kgf/cm2.