N-formyl vortioxetine and preparation method thereof and solid preparation of vortioxetine

Patent metadata

Field	Value
Publication number	US-11707461-B2
Application number	US-201716647847-A
Country	US
Kind code	B2
Filing date	Sep 20, 2017
Priority date	Sep 20, 2017
Publication date	Jul 25, 2023
Grant date	Jul 25, 2023

Abstract

Disclosed is N-formyl vortioxetine, and also disclosed is a method for preparing the N-formyl vortioxetine and a stable solid preparation of vortioxetine.

First claim

The invention claimed is:

1. A method for preparing a storage-stable pharmaceutical composition comprising vortioxetine, the method comprising:
combining vortioxetine or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, wherein the pharmaceutically acceptable excipient is free of a reducing sugar material; and
dry granulating the vortioxetine or the pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable excipient;
wherein the storage-stable pharmaceutical composition after storage over 6 months at 40° C. and 75% relative humidity contains no greater than 0.2% of N-formyl vortioxetine;
wherein the storage-stable pharmaceutical composition consists of following components, based on the total weight of the composition:

vortioxetine hydrobromide 16.95% by weight,
microcrystalline cellulose 15.0% by weight,
mannitol 58.55% by weight,
hydroxypropyl cellulose 3.0% by weight,
sodium carboxymethyl starch 3.0% by weight,
talcum powder 2.0% by weight, and
magnesium stearate 1.5% by weight;
or the storage-stable pharmaceutical composition consists of following components, based on the total weight of the composition:

vortioxetine hydrobromide 16.95% by weight,
mannitol 71.55% by weight,
copovidone 5.0% by weight,
sodium carboxymethyl starch 3.0% by weight,
talcum powder 2.0% by weight, and
magnesium stearate 1.5% by weight.

2. The method of claim 1 , wherein:
the step of combining comprises;
uniformly mixing vortioxetine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, and
pressing a mixture of step 1) into a compact;

the step of dry granulating comprises 3) converting the compact into granules using dry granulation; and
the method further comprises 4) compressing the granules into tablets or filling the granules into capsules.

3. The method of claim 1 , wherein the storage-stable pharmaceutical composition after storage over 6 months at 40° C. and 75% relative humidity contains no greater than 0.1% of N-formyl vortioxetine.

Assignees

• Zhejiang Huahai Pharm Co Ltd

Inventors

• Lin Jinsheng
• Huang Tianpei
• Lan Feifei
• Xu Xiaoyan
• Hu Libin
• Li Dan
• Zhu Wenquan
• Li Min
• Wang Zhiyun

Classifications

• A61K31/4965 Primary

  Non-condensed pyrazines · CPC title

• A61K47/38

  Cellulose; Derivatives thereof · CPC title

• C07D295/108 Primary

  to an acyclic saturated chain · CPC title