Hot-melt extrusion of modified release multi-particulates

Patent metadata

Field	Value
Publication number	US-9827202-B2
Application number	US-201514873176-A
Country	US
Kind code	B2
Filing date	Oct 1, 2015
Priority date	Aug 20, 2008
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

Abstract

The present invention includes compositions and methods of making a modified release pharmaceutical formulation and a method of preparation for the embedding of modified release multi-particulates into a polymeric or wax-like matrix. The modified release multi-particulates comprise an effective amount of a therapeutic compound having a known or desired drug-release profile. Modified release multi-particulates may include a polymeric coat or may be incorporated into particle or core material. The polymer matrix comprises a thermoplastic polymer or lipophilic carrier or a mixture thereof that softens or melts at elevated temperature and allows the distribution of the modified release multi-particulates in the polymer matrix during thermal processing. Formulation compounds and processing conditions are selected in a manner to preserve the controlled release characteristics and/or drug-protective properties of the original modified release multi-particulates.

First claim

What is claimed is:

1. A modified release pharmaceutical composition comprising an extruded thermoplastic polymer matrix comprised of a poly(ethylene oxide) or a poly(ethylene oxide)-polypropylene oxide) copolymer in which modified release multi-particulate pellets are uniformly disposed, wherein the modified release multi-particulate pellets have a particle size of from 300 to 800 μm or an average particle size of from 300 to 3000 μm, and further wherein individual multi-particulate pellets comprise a modified release polymer matrix or a modified release polymer coating, and also further comprise an effective amount of one or more therapeutic compounds.

2. The composition of claim 1 , wherein the extruded thermoplastic polymer matrix comprises at least 80% intact multi-particulate pellets by weight.

3. The composition of claim 1 , wherein the extruded thermoplastic polymer matrix is hydrophilic.

4. The composition of claim 1 , wherein a polymer of the extruded thermoplastic polymer matrix has a molecular weight of less than 1,000,000.

5. The composition of claim 1 , wherein the multi-particulate pellets comprise 5 to 70 weight percent of the composition.

6. The composition of claim 1 , wherein the multi-particulate pellets comprise an effective amount of 5 to 80 weight percent of one or more therapeutic compounds.

7. The composition of claim 1 , wherein the modified release polymer is an enteric drug release polymer.

8. The composition of claim 1 , wherein the multi-particulate pellets comprise between 10% to 60% (w/w) of the modified release polymer.

9. The composition of claim 1 , wherein the multi-particulate pellets are film-coated drug granules, film-coated drug-loaded pellets or film-coated drug-layered nonpareils.

10. The composition of claim 1 , wherein the multi-particulate pellets, or a component thereof, does not dissolve in the extruded thermoplastic polymer matrix.

11. The composition of claim 7 , wherein less than 10% of the one or more therapeutic compounds will be released in acidic media from the composition, and wherein 80% of the one or more therapeutic compounds will be released in media pH above 6.8 according to USP 31, method 711 for delayed-release dosage forms method A.

12. The composition of claim 1 , wherein the multi-particulate pellets have an average particle size of from 300 to 3000 μm.

13. The composition of claim 12 , wherein the multi-particulate pellets have a particle size of from 300 to 800 μm and an average particle size of from about 300 to 3000 μm.

14. The composition of claim 1 , wherein the multi-particulate pellets have a particle size of from 300 to 800 μm.

15. The composition of claim 1 , further defined as a tablet.

16. The composition of claim 1 , wherein the modified release polymer is further defined as immediate, extended, sustained or delayed release polymer.

Assignees

• Univ Texas

Inventors

• Mcginity James W
• Schilling Sandra U

Classifications

• A61P11/08

  Bronchodilators · CPC title

• B29C48/00

  Extrusion moulding, i.e. expressing the moulding material through a die or nozzle which imparts the desired form; Apparatus therefor (extrusion blow-moulding B29C49/04) · CPC title

• B29K2105/0035

  Medical or pharmaceutical agents · CPC title

• A61K9/1694

  resulting in granules or microspheres of the matrix type containing more than 5% of excipient · CPC title

• A61K9/2081

  with microcapsules or coated microparticles according to A61K9/50 · CPC title