Apparatus for preparing biodegradable microparticle formulations containing pharmaceutically active agents

• US 7,261,529 B2
• Filed: 09/07/2005
• Issued: 08/28/2007
• Est. Priority Date: 09/07/2005
• Status: Active Grant

• Current Assignee: Alcon Incorporated, Southwest Research Institute
• Original Assignee: Southwest Research Institute
• Inventors: Vail, Neal K., Zwiener, Albert M., Persyn, Joseph T., Barlow, Darren E., Slovin, Eliot M., McDonough, Joseph A.
• Primary Examiner(s): Davis; Robert
• Assistant Examiner(s): Ewald; Maria Veronica
• Application Number:
  US11/221,337
• Publication Number:
  US 20070054002A1
• Time in Patent Office: 720 Days
• Field of Search: 425/6, 425/7, 425/8, 264/8, 264/9, 264/14, 264/4.1
• US Class Current: 425/8
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: B01J 2/10 in stationary drums or troughs, provided with kneading or mixing appliances

Abstract

This invention is directed to an apparatus and method for producing microparticles comprising pharmacologically active agents and biodegradable polymers. The apparatus includes a spinning disk containing a reservoir in the center thereof and a flat inclined surface. The apparatus optionally includes serrations and/or a flat surface beneath the periphery of the disk that is parallel to the rotational axis of the disk. The invention is also directed to a method for producing microparticles containing pharmacologically active agents, using the spinning disk apparatus. Formulations containing ophthalmically active agents are provided. Formulations exhibiting zero order release rates are also described.

Claims

1. A spinning disk apparatus for producing microparticles comprising a substantially circular spinning disk, wherein the spinning disk comprises:

(A) an inner peripheral edge;

(B) an outer peripheral edge;

(C) a substantially smooth annular disk surface extending between the inner peripheral edge and the outer peripheral edge, wherein

(i) the outer peripheral edge defines a first diameter of the annular disk surface,

(ii) the annular disk surface has a second diameter defined by the area circumscribed by the inner peripheral edge, wherein the area circumscribed by the inner peripheral edge is disposed substantially in a center portion of the spinning disk, and

(iii) the annular disk surface extending between the inner peripheral edge and the outer peripheral edge comprises a substantially flat incline; and

(D) a reservoir disposed in the area circumscribed by the inner peripheral edge of the annular disk surface, wherein

(i) the reservoir comprises a top portion thereof defined by the second diameter, and

(ii) the reservoir comprises a cross-sectional area defined by a third diameter, located between the bottom of the reservoir and the top portion of the reservoir, wherein the third diameter is greater than the second diameter.

2. The spinning disk apparatus of claim 1, wherein the first diameter of the annular disk surface is between about 10 mm and about 300 mm.

3. The spinning disk apparatus of claim 1, wherein the first diameter of the annular disk surface and the second diameter of the annular disk surface are in a ratio between about 300:

1 and about 2;

1.

4. The spinning disk apparatus of claim 1, wherein the third diameter defining the cross-sectional area of the reservoir and the second diameter of the annular disk surface are in a ratio between about 20:

1 and about 1.05;

1.

5. The spinning disk apparatus of claim 1, wherein the substantially flat incline comprises an angle between about 5 degrees and about 45 degrees.

6. The spinning disk apparatus of claim 5, wherein the substantially flat incline comprises an angle between about 15 degrees and about 30 degrees.

7. The spinning disk apparatus of claim 1, wherein the outer peripheral edge of the annular disk surface comprises serrations.

8. The spinning disk apparatus of claim 7, wherein the serrations have a length between about 0 μ

m and about 5,000 μ

m.

9. The spinning disk apparatus of claim 8, wherein the serrations have a length between about 500 μ

m and about 1,500 μ

m.

10. The spinning disk apparatus of claim 7, wherein the serrations define an angle therebetween between about 105 degrees and about 15 degrees.

11. The spinning disk apparatus of claim 10, wherein the serrations define an angle therebetween between about 65 degrees and about 20 degrees.

12. The spinning disk apparatus of claim 1, wherein the spinning disk comprises a substantially flat surface beneath the annular disk surface and proximate the outer peripheral edge thereof, wherein the substantially flat surface lies in a plane that is substantially parallel to the rotational axis of the spinning disk.

13. The spinning disk apparatus of claim 12, wherein the substantially flat surface has a length between about 1 mm and about 10 mm.

14. The spinning disk apparatus of claim 1, wherein the apparatus comprises a process chamber, wherein the process chamber comprises a material selected from the group consisting of a thermally controllable material, a low thermal conductivity material, and combinations thereof.

15. The spinning disk apparatus of claim 14, wherein the thermally controllable material comprises jacketed stainless steel.

16. The spinning disk apparatus of claim 14, wherein the low thermal conductivity material comprises plastic.

17. The spinning disk apparatus of claim 14, wherein the process chamber comprises a cone bottom tank, wherein the cone bottom tank comprises a material selected from the group consisting of a thermally controllable material, a low thermal conductivity material, and combinations thereof.

18. The spinning disk apparatus of claim 17, wherein the thermally controllable material comprises jacketed stainless steel.

19. The spinning disk apparatus of claim 17, wherein the low thermal conductivity material comprises plastic.

20. The spinning disk apparatus of claim 1, wherein the apparatus comprises a sample collection system comprising a cyclone separator, wherein the cyclone separator comprises a material selected from the group consisting of a thermally controllable material, a low thermal conductivity material, and combinations thereof.

21. The spinning disk apparatus of claim 20, wherein the thermally controllable material comprises jacketed stainless steel.

22. The spinning disk apparatus of claim 20, wherein the low thermal conductivity material comprises plastic.

23. The spinning disk apparatus of claim 1, wherein the third diameter of the reservoir is disposed proximate the bottom of the reservoir.