Method for preparing pharmaceutical composition comprising quinoline derivative or salt thereof

Patent metadata

Field	Value
Publication number	US-10722469-B2
Application number	US-201716071572-A
Country	US
Kind code	B2
Filing date	Jan 23, 2017
Priority date	Jan 27, 2016
Publication date	Jul 28, 2020
Grant date	Jul 28, 2020

Abstract

The present invention provides a method for preparing a pharmaceutical composition containing a quinoline derivative or a salt thereof. Specifically, the invention provides a method for preparing a pharmaceutical composition containing (R,E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(1-methylpyrrolidin-2-yl)-propeneamide or a pharmaceutically acceptable salt thereof. The method uses a wetting agent containing at least one organic solvent for a wet granulation in a preparation process of the pharmaceutical composition. The pharmaceutical composition prepared using the method has a uniform distribution of grain sizes during the preparation process and a property of rapid and uniform dissolution.

First claim

What is claimed is:

1. A method for preparing a pharmaceutical composition, comprising:
(1) mixing the active ingredient (R,E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(1-methylpyrrolidin-2-yl)-propeneamide, or a pharmacologically acceptable salt thereof with a wetting agent and one or more additional ingredients to obtain a mixture,
(2) granulating the mixture to obtain granules,
(3) drying the granules to obtain dried granules, and
(4) tableting the dried granules into tablets or filling dried granules into capsules to obtain the pharmaceutical composition,
wherein:
the wetting agent is a mixed solvent of ethanol and water, the ethanol is present in an amount of 50-80% by weight relative to the total weight of the wetting agent, and
the pharmaceutical composition further comprises:
1) 2-20 wt % of a disintegrant, wherein the disintegrant is cross-linked polyvinylpyrrolidone;
2) 5-80 wt % of a filler, wherein the filler is one or more selected from the group consisting of lactose and microcrystalline cellulose;
3) 0.5-15 wt % of a binder, wherein the binder is one or more selected from the group consisting of polyvinylpyrrolidone, hydroxypropyl methyl cellulose and hydroxypropyl cellulose; and
4) 0.5-5 wt % of a lubricant, wherein the lubricant is one or more selected from the group consisting of magnesium stearate and talc,
wherein the pharmaceutical composition provides a dissolution rate such that at least 80% of the active ingredient is released from the pharmaceutical composition within 30 minutes when measured in a dissolution medium containing 0.1 mol/L hydrochloric acid solution at 37±0.5° C. and at a paddle speed of 50 rpm.

2. A pharmaceutical composition prepared by the method according to claim 1 .

3. A method of preparing a tablet, comprising:
(1) mixing the following ingredients to obtain a first mixture:
(i) 10%-50 wt % of the active ingredient (R,E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(1-methylpyrrolidin-2-yl)-propeneamide or a pharmacologically acceptable salt thereof;
(i) 2-20 wt % of a cross-linked polyvinylpyrrolidone;
(ii) 5-80 wt % of a filler comprising one or more agents selected from the group consisting of lactose and microcrystalline cellulose; and
(iii) 0.5-15 wt % of a binder comprising one or more agents selected from the group consisting of polyvinylpyrrolidone, hydroxypropyl methyl cellulose and hydroxypropyl cellulose;
(2) granulating the first mixture using a wetting agent to obtain wet granules, wherein the wetting agent contains a mixed solvent of ethanol and water, and ethanol is present in an amount of 50-95% by weight relative to the total weight of the wetting agent;
(3) drying the granules to obtain dried granules,
(4) mixing the dried granules with 0.5-5 wt % of a lubricant comprising one or more agent selected from the group consisting of magnesium stearate and talc to obtain a second mixture; and
(4) tableting the second mixture into the tablets.

4. A pharmaceutical composition prepared by the method according to claim 3 .

Assignees

• Jiangsu Hengrui Medicine Co

Inventors

• Lu Yun
• Zhang Xinhua
• Wang Chenyang

Classifications

• A61K9/4866

  Organic macromolecular compounds · CPC title

• A61K9/2095

  Tabletting processes · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K9/2027

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title