Drug/polymer composite materials and methods of making the same

• US 20070009564A1
• Filed: 06/22/2005
• Published: 01/11/2007
• Est. Priority Date: 06/22/2005
• Status: Abandoned Application

• Current Assignee: James Deyoung, James Mcclain
• Original Assignee: Micell Technologies Inc.
• Inventors: DeYoung, James, McClain, James
• Application Number:
  US11/158,724
• Publication Number:
  US 20070009564A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: Y02P 20/54 using solvents, e.g. supercritical solvents or ionic liquids

Abstract

A method of forming a drug/polymer composite material is carried out by combining a drug material with a polymer material under pressure in the presence of a compressed gas solvent (e.g., carbon dioxide) to form the drug/polymer composite material. Drug/polymer composite materials and shaped articles (e.g., subcutaneous drug depots) which may be produced by a process are also described, along with methods of use thereof.

Claims

1. A method of forming a drug/polymer composite material, comprising the steps of:

(a) mixing a solid particulate drug material with a solid particulate polymer material, and optionally with a pharmaceutical excipient, to form a particle mixture of polymer particles and interspersed drug particles; and

then

(b) combining said particle mixture with a compressed gas solvent at a pressure sufficient to reduce the viscosity of said polymer material, fuse said polymer particles to one another and capture said drug particles therebetween and form a drug/polymer composite material from said particulate mixture.

2. The method of claim 1, wherein said combining step (b) is carried out in a mold so that a shaped article of said drug/polymer composite material is thereby produced.

3. The method of claim 2, wherein said shaped article is a stent, drug depot, or biomedical implant.

4. The method of claim 1, further comprising the step:

(c) forming a shaped article from said drug/polymer composite material.

5. The method of claim 4, wherein said combining step (b) is carried out in an extruder.

6. The method of claim 4, wherein said forming step (c) is carried out by molding.

7. The method of claim 4, wherein said forming step (c) is carried out by coating a pre-formed substrate with said drug/polymer composite material.

8. The method of claim 4, wherein said shaped article is a stent, drug depot, or biomedical implant.

9. The method of claim 1, wherein said drug is in crystalline or amorphous form.

10. The method of claim 1, wherein said drug is a protein or peptide.

11. The method of claim 1, wherein said composite material comprises:

from 0.01 percent to 50 percent by weight of drug;

from 50 to 99.99 percent by weight of polymer; and

optionally, from 0.01 to 30 percent by weight of pharmaceutical excipient.

12. The method of claim 1, wherein said pharmaceutical excipient is absent.

13. The method of claim 1, wherein said pharmaceutical excipient is present.

14. The method of claim 13, wherein said pharmaceutical excipient is selected from the group consisting of adjuvants, surfactants, stabilizers, morphology modifiers, porogens, diluents, carriers, solubilizers, antioxidants, lubricants, binders, disintigrants, and mixtures thereof.

15. The method of claim 13, wherein said pharmaceutical excipient is a hydrophobically derivatized carbohydrate.

16. The method of claim 15, wherein said hydrophobically derivatized carbohydrate is selected from the group consisting of sorbitol hexaacetate, alpha-glucose pentaacetate, beta-glucose pentaacetate, 1-0-Octyl-beta-D-glucose tetraacetate, trehalose octaacetate, tetralose octapropionate, trehalose octa-3,3,dimethylbutyrate, trehalose diisobutyrate hexaacetate, trehalose octaisobutyrate, lactose octaacetate, sucrose octaacetate, cellobiose octaacetate, raffinoso undecaacetate, sucrose octapropanoate, cellobiose octapropanoate, raffinose undecapropanoate, tetra-0-methyl trehalose, trehalose octapivalate, trehalose hexaacetate dipivalate and di-0-methyl-hexa-0-actyl sucrose and mixtures thereof.

17. The method of claim 1, further comprising the step of coating said composite material with a secondary material.

18. The method of claim 1, wherein said excipient is a porogen, said method further comprising the step of contacting said composite material to a solvent to at least partially solubilize said porogen and form pores in said composite material.

19. A drug/polymer composite material produced by the process of claim 1.

20. The composite of claim 19, wherein said composite is porous.

21. A method of treating a subject with a drug, comprising administering a drug/polymer composite material of claim 19 to said subject in an amount effective to treat said subject with said drug.

22. A shaped article comprising a drug/polymer composite material of claim 19.

23. The shaped article of claim 22, wherein said shaped article is a stent, drug depot, or biomedical implant.

24. The shaped article of claim 22, wherein said shaped article is a porous subcutaneous drug depot.