SUSPENSION DELIVERY SYSTEM FOR THE SUSTAINED AND CONTROLLED LOCAL RELEASE OF PHARMACEUTICALS

• US 20110129541A1
• Filed: 08/27/2010
• Published: 06/02/2011
• Est. Priority Date: 10/27/2003
• Status: Abandoned Application

• Current Assignee: pSivida US, Inc
• Original Assignee: Control Delivery Systems Inc. (EyePoint Pharmaceuticals, Inc.)
• Inventors: Guo, Hong, Ashton, Paul, Chen, Jianbing
• Application Number:
  US12/870,618
• Publication Number:
  US 20110129541A1
• Time in Patent Office: Days
• US Class Current: 424/499
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• 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 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The invention relates to a novel suspension delivery system for the sustained and controlled release of pharmaceuticals. Methods of preparation and use are also disclosed.

Claims

1. A drug delivery system for parenteral administration comprising:

(a) a pellet, wherein said pellet comprises at least one agent admixed with at least one super disintegrant compound, and

(b) an aqueous medium suitable for administering the at least one agent and at least one super disintegrant compound to a patient; and

wherein the pellet and aqueous medium are sterile and the at least one agent is a codrug comprising a non-steroidal anti-inflammatory drug and an opioid analgesic and the at least one disintegrant is selected from crospovidone, carmellose, directly compressible starches, modified starches, natural starches, and modified celluloses.

3. The drug delivery system according to claim 1, wherein the system is substantially pyrogen-free.

4. The drug delivery system of claim 1, wherein the at least one agent has a solubility of less than 1 mg/mL in the aqueous medium.

5. The drug delivery system of claim 1, having a release profile sufficient to deliver the at least one agent at a therapeutically effective dose over a period of at least 24 hours.

6. The drug delivery system of claim 1, having a release profile sufficient to deliver the at least one agent at a therapeutically effective dose over a period of at least 1 week.

7. The drug delivery system of claim 1, wherein the weight of the disintegrant compound is less than 10% of the weight of the pellet.

9. The drug delivery system of claim 1, wherein the pellet is less than 3 mm in diameter and less than 2 mm in height.

10. The drug delivery system of claim 1, wherein the pellet weighs less than 7 mg.

11. The drug delivery system of claim 1, wherein at least 90% of the pellet by weight is the at least one agent.

12. The drug delivery system of claim 1, wherein the at least one super disintegrant is sodium starch glycolate or croscarmellose sodium.

13. The drug delivery system of claim 1, wherein the at least one super disintegrant is croscarmellose sodium.

14. The drug delivery system of claim 1, wherein the pellet further includes at least one pharmaceutically acceptable carrier.

15. The drug delivery system of claim 14, wherein the pharmaceutically acceptable carrier is magnesium stearate.

16. The drug delivery system of claim 1, wherein the aqueous medium includes hyaluronic acid.

17. The drug delivery system of claim 1, wherein the aqueous medium includes saline solution.

18. The drug delivery system of claim 1, wherein the at least one agent has a decomposition half-life of less than about 1 month in aqueous solution at pH 7.4 and 25°

C.

19. The drug delivery system of claim 1, wherein the at least one agent has a decomposition half-life of less than about 1 week in aqueous solution at pH 7.4 and 25°

C.

20. The drug delivery system of claim 1, wherein the at least one agent has a decomposition half-life of less than about 24 hours in aqueous solution at pH 7.4 and 25°

C.

21. The drug delivery system of claim 1, wherein the codrug includes a non-steroidal, anti-inflammatory drug covalently linked to an opioid analgesic.

22. The drug delivery system of claim 21, wherein the non-steroidal, anti-inflammatory drug is diclofenac or ketorolac and the opioid analgesic is morphine.

23. The drug delivery system of claim 1, wherein the disintegrant compound is a super disintegrant and is selected from one or more of carboxymethylcellulose, sodium starch glycolate, and cross-linked povidone.

24. The drug delivery system of claim 1, wherein the pellet and aqueous medium form a suspension when combined.

25. The drug delivery system of claim 1, wherein the pellet is greater than 1 mm and less than 10 mm in height.

2. A drug delivery system for parenteral administration, comprising a pellet and an aqueous medium, the pellet having at least one agent in admixture with at least one disintegrant compound, wherein the pellet is dispersed in an aqueous medium to form a suspension suitable for administration to a patient;

and the pellet and aqueous medium are sterile.

8. The drug delivery system of claim 2, wherein the pellet is dispersed in the aqueous medium within about 15 minutes of administering at least a portion of the suspension to a patient.