Pharmaceutical composition comprising amide derivative inhibiting the growth of cancer cells and non-metallic salt lubricant

Patent metadata

Field	Value
Publication number	US-9731022-B2
Application number	US-201214124436-A
Country	US
Kind code	B2
Filing date	May 18, 2012
Priority date	Jun 7, 2011
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

Disclosed is a pharmaceutical composition comprising an amide derivative or a pharmaceutically acceptable salt thereof and a non-metallic salt lubricant, which can be used as an effective cancer cell-growth inhibitor owing to its enhanced storage stability with no quality changes over time.

First claim

What is claimed is:

1. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient and a non-metallic salt lubricant:

wherein the non-metallic salt lubricant is selected from the group consisting of glyceryl behenate, glyceryl palmitostearate, glyceryl monostearate, glyceryl trimyristate, glyceryl tristearate, sucrose fatty acid ester, palmitic acid, palmitoyl alcohol, stearic acid, stearyl alcohol, fumaric acid, polyethyleneglycol 4000, polyethyleneglycol 6000, polytetrafluoroethylene, starch, and a mixture thereof, wherein the composition is a solid compressed composition, and wherein the composition is free of metallic salt lubricants.

2. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is sucrose fatty acid ester.

3. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is contained in an amount ranging from 0.1 to 100 parts by weight based on 1 part by weight of the compound of formula (I) or said pharmaceutically acceptable salt.

4. The pharmaceutical composition of claim 1 , which further comprises a pharmaceutically acceptable additive selected from the group consisting of a diluent, a binder, a disintegrant, and a mixture thereof.

5. The pharmaceutical composition of claim 4 , wherein said diluent is contained in an amount ranging from 20% to 95% by weight based on the total weight of the composition.

6. The pharmaceutical composition of claim 4 , wherein said binder is contained in an amount ranging from 1% to 10% by weight based on the total weight of the composition.

7. The pharmaceutical composition of claim 4 , wherein said disintegrant is contained in an amount ranging from 1% to 30% by weight based on the total weight of the composition.

8. The pharmaceutical composition of claim 1 , which is coated with a coating substrate selected from the group consisting of a rapid release coating substrate, an enteric coating substrate, and a sustained release coating substrate.

9. The pharmaceutical composition of claim 8 , wherein said coating substrate is selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymer, (meth)acrylic acid copolymer, phthalic acid hydroxypropyl methylcellulose, phthalic acid cellulose acetate, cellulose acetate, ethyl cellulose, polyvinyl acetate, and a mixture thereof.

10. The pharmaceutical composition of claim 1 , which comprises a compound of formula (II) less than 0.5% by weight under extreme conditions kept in an airtight high density polyethylene (HDPE) container at 60° C. for 4 weeks, or under accelerated conditions kept in an airtight HDPE container at 40° C. and 75% RH for 6 months:

11. A unit dosage composition comprising the pharmaceutical composition of claim 1 , wherein said compound of formula (I) or said pharmaceutically acceptable salt is contained in an amount ranging from 0.1 mg to 100 mg.

12. A method for preparing a formulation of the pharmaceutical composition of claim 1 , which comprises the steps of:
(1) mixing a compound of formula (I) or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable additive, and granulating the mixture to obtain granules;
(2) mixing the granules prepared in step (1) with a pharmaceutically acceptable additive, and adding a non-metallic salt lubricant thereto to obtain mixed granules; and
(3) subjecting the mixed granules prepared in step (2) to a compression step:

wherein the non-metallic salt lubricant is selected from the group consisting of glyceryl behenate, glyceryl palmitostearate, glyceryl monostearate, glyceryl trimyristate, glyceryl tristearate, sucrose fatty acid ester, palmitic acid, palmitoyl alcohol, stearic acid, stearyl alcohol, fumaric acid, polyethyleneglycol 4000, polyethyleneglycol 6000, polytetrafluoroethylene, starch, and a mixture thereof.

13. The method of claim 12 , which further comprises the step of coating the formulation prepared in step (3) with a coating substrate selected from the group consisting of a rapid release coating substrate, an enteric coating substrate, and a sustained release coating substrate.

14. A method for stabilizing a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, comprising adding a non-metallic salt lubricant to the pharmaceutical composition:

wherein the non-metallic salt lubricant is selected from the group consisting of glyceryl behenate, glyceryl palmitostearate, glyceryl monostearate, glyceryl trimyristate, glyceryl tristearate, sucrose fatty acid ester, palmitic acid, palmitoyl alcohol, stearic acid, stearyl alcohol, fumaric acid, polyethyleneglycol 4000, polyethyleneglycol 6000, polytetrafluoroethylene, starch, and a mixture thereof, wherein the composition is a solid compressed composition, and wherein the composition is free of metallic salt lubricants.

15. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is stearic acid.

16. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is glyceryl behenate.

17. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is glyceryl palmitostearate.

18. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is starch.

19. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is PEG 6000.

20. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is glyceryl monostearate.

21. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is palmitoyl alcohol.

22. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is stearyl alcohol.

23. The pharmaceutical composition of claim 1 , wherein said non-metallic salt lubricant is fumaric acid.

Assignees

• Kim Yong Il
• Kim Kyeong Soo
• Kim Jin Cheul
• Kim Yo Han
• Park Jae Hyun
• Woo Jong Soo
• Hanmi Pharm Ind Co Ltd

Inventors

• Kim Yong Il
• Kim Kyeong Soo
• Kim Jin Cheul
• Kim Yo Han
• Park Jae Hyun
• Woo Jong Soo

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title

• A61K47/44 Primary

  Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14) · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K9/2009

  Inorganic compounds · CPC title