Solid dispersions of insoluble drug and preparation method thereof

Patent metadata

Field	Value
Publication number	US-9724335-B2
Application number	US-201615394481-A
Country	US
Kind code	B2
Filing date	Dec 29, 2016
Priority date	Nov 7, 2012
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

The present invention relates to a solid dispersion characterized in that it comprises carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester as an active ingredient and a water-soluble polymer having a glass transition temperature lower than the melting point of the active ingredient as a carrier, and it is prepared via melt extrusion. The solid dispersion of the present invention remarkably increases the solubility and dissolution rate of the active ingredient which is an insoluble drug to efficiently improve the bioavailability when it is orally administered.

First claim

What is claimed is:

1. A method for preparing a solid dispersion, comprising:
mixing 10 to 50 wt % of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester or a pharmaceutically acceptable salt thereof, 45 to 85 wt % of a water-soluble polymer having a glass transition temperature lower than the melting point of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester, and 1 to 5 wt % of a plasticizer, and
melt-extruding the mixture at a temperature lower than the melting point of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester,
wherein the water-soluble polymer is selected from polyvinylpyrrolidone, hypromellose acetate succinate and a combination thereof, and
the plasticizer is selected from the group consisting of D-alpha-tocopheryl polyethylene glycol 1000 succinate, polyethylene glycol 400, and a combination thereof.

2. The method of claim 1 , wherein the mixture is melted when it passes through four (4) or more heating blocks, wherein a temperature of the heating blocks is sequentially lowered.

3. The method of claim 2 , wherein the heating blocks consist of a first, a second, a third, and a fourth heating blocks,
wherein a temperature of the first heating block is controlled to 160 to 145° C.,
wherein a temperature of the second heating block is controlled to 144 to 120° C.,
wherein a temperature of the third heating block is controlled to 119 to 80° C., and
wherein a temperature of the fourth heating block is controlled to 79 to 70° C.

4. The method of claim 1 , wherein the water-soluble polymer is contained in the amount of about 70 to 85 wt % based on the total weight of the mixture.

5. The method of claim 1 , wherein the plasticizer is contained in the amount of about 1 wt % based on the total weight of the mixture.

6. The method of claim 1 , wherein the mixture comprises 50 to 85 wt % of polyvinylpyrrolidone.

7. The method of claim 1 , wherein the mixture comprises:
about 30 wt % of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-lmethyl ester,
about 69 wt % of polyvinylpyrrolidone, and
about 1 wt % of D-alpha-tocopheryl polyethylene glycol 1000 succinate.

8. The method of claim 1 , wherein the mixture comprises:
about 30 wt % of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester,
about 69 wt % of polyvinylpyrrolidone, and
about 1 wt % of polyethylene glycol 400.

9. The method of claim 1 , wherein the mixture comprises:
about 15 wt % of carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester,
about 84 wt % of hypromellose acetate succinate, and
about 1 wt % of polyethylene glycol 400.

Assignees

• Sk Biopharmaceuticals Co Ltd

Inventors

• Baek Myoung Ki
• Pegan Augustin

Classifications

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07D261/08

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• A61K9/146 Primary

  with organic macromolecular compounds · CPC title

• A61K31/42 Primary

  Oxazoles · CPC title