Solid dispersion comprising a highly substituted hydroxyalkyl methylcellulose

Patent metadata

Field	Value
Publication number	US-9962446-B2
Application number	US-201314413241-A
Country	US
Kind code	B2
Filing date	Jul 12, 2013
Priority date	Jul 17, 2012
Publication date	May 8, 2018
Grant date	May 8, 2018

Abstract

A solid dispersion comprising at least one active ingredient in at least one hydroxyalkyl methylcellulose having a DS of from 1.0 to 2.7 and an MS of from 0.40 to 1.30, wherein DS is the degree of substitution of methoxyl groups and MS is the molar substitution of hydroxyalkoxyl groups, can be produced by extrusion or spray-drying.

First claim

What is claimed is:

1. A solid dispersion comprising at least one active ingredient in at least one hydroxyalkyl methylcellulose having a DS of from 1.4 to 2.7, an MS of from 0.60 to 1.10 and a sum of DS and MS of at least 2.5, wherein DS is the degree of substitution of methoxyl groups and MS is the molar substitution of hydroxyalkoxyl groups, wherein the active ingredient is a drug having a Tm/Tg ratio of more than 1.15 and up to 1.5, wherein Tm is the melting temperature and Tg is the glass transition temperature, each in Kelvin.

2. The solid dispersion of claim 1 wherein said at least one hydroxyalkyl methylcellulose has a sum of DS and MS of from 2.5 to 3.2.

3. The solid dispersion of claim 1 wherein said at least one hydroxyalkyl methylcellulose has a viscosity of 105 to 164,000 mPa·s, measured as a 2.0 weight percent solution in water at 20° C.

4. The solid dispersion of claim 3 wherein said at least one hydroxyalkyl methylcellulose has a DS of from 1.6 to 2.1.

5. The solid dispersion of claim 4 wherein the sum of the DS and MS is from 2.5 to 3.2.

6. The solid dispersion of claim 1 in the form of strands, pellets, granules, pills, tablets, caplets, microparticles, fillings of capsules or injection molded capsules or in the form of a powder, film, paste, cream, suspension or slurry.

7. An extruded solid dispersion of claim 1 .

8. A process for producing a solid dispersion comprising the steps of
blending a) at least one hydroxyalkyl methylcellulose having a DS of from 1.4 to 2.7, an MS of from 0.60 to 1.10 and a sum of DS and MS of at least 2.5, wherein DS is the degree of substitution of methoxyl groups and MS is the molar substitution of hydroxyalkoxyl groups, b) one or more active ingredients and c) one or more optional additives, and
subjecting the blend to extrusion at a temperature of from 90 to 190° C., wherein the active ingredient is a drug having a Tm/Tg ratio of more than 1.15 and up to 1.5, wherein Tm is the melting temperature and Tg is the glass transition temperature, each in Kelvin.

9. The process of claim 8 wherein the combined amounts of said at least one hydroxyalkyl methylcellulose a) and said one or more active ingredients b) are at least 70 percent, based on the total weight of the blend.

10. A process for producing a solid dispersion comprising the steps of
blending a) at least one hydroxyalkyl methylcellulose having a DS of from 1.4 to 2.7, an MS of from 0.60 to 1.10 and a sum of DS and MS of at least 2.5, wherein DS is the degree of substitution of methoxyl groups and MS is the molar substitution of hydroxyalkoxyl groups, b) one or more active ingredients, c) one or more optional additives, and d) an organic liquid diluent to prepare a liquid composition, and
removing liquid diluent from the liquid composition, wherein the active ingredient is a drug having a Tm/Tg ratio of more than 1.15 and up to 1.5, wherein Tm is the melting temperature and Tg is the glass transition temperature, each in Kelvin.

11. The process of claim 10 wherein the liquid composition is subjected to spray-drying.

12. The process of claim 10 wherein the composition comprises water as an optional additive and the composition comprises more than 50 weight percent of an organic liquid diluent and less than 50 weight percent of water, based on the total weight of organic liquid diluent and water, and wherein organic liquid diluent and water are removed from the liquid composition.

13. An extruded solid dispersion of claim 4 .

14. The process of claim 9 wherein said at least one hydroxyalkyl methylcellulose has a DS of from 1.6 to 2.1.

15. The process of claim 11 wherein said at least one hydroxyalkyl methylcellulose has a DS of from 1.6 to 2.1.

16. The solid dispersion of claim 4 wherein the sum of the DS and MS is from 2.5 to 2.9.

17. The process of claim 14 wherein the sum of the DS and MS is from 2.5 to 2.9.

Assignees

• Dow Global Technologies Llc

Inventors

• Grasman Nicholas S
• Guillaudeu Steven J
• Hall Mark J
• Shrestha Uma
• Rose Maureen L
• Porter Iii William W
• Spaulding Wesley J
• O'Donnell Kevin P
• Rogers True L

Classifications

• A61K9/4891

  Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004) · CPC title

• A61K31/58

  containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) · CPC title

• A61K9/146 Primary

  with organic macromolecular compounds · CPC title

• A61K31/4166

  having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin · CPC title

• A61K47/38 Primary

  Cellulose; Derivatives thereof · CPC title