METHOD OF FORMING PROLONGED-RELEASE INJECTABLE STEROIDS

• US 20110081420A1
• Filed: 05/03/2010
• Published: 04/07/2011
• Est. Priority Date: 10/07/2009
• Status: Abandoned Application

• Current Assignee: Zyga Technology, Inc. (Surgalign Holdings, Inc.)
• Original Assignee: Zyga Technology, Inc. (Surgalign Holdings, Inc.)
• Inventors: Barrows, Thomas Harry
• Application Number:
  US12/772,358
• Publication Number:
  US 20110081420A1
• Time in Patent Office: Days
• US Class Current: 424/499
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• 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 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1682 Processes
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Abstract

A method of forming prolonged-release injectable steroids. The method includes providing a steroid composition, a bioabsorbable polymer and a solvent. A solution is formed from the steroid composition, the bioabsorbable polymer and the solvent. Droplets are formed from the solution. The solvent is removed from the droplets to cause the droplets to form microspheres.

Claims

1. A method of forming prolonged-release injectable steroids comprising:

providing a steroid composition;

providing a bioabsorbable polymer;

providing a solvent;

forming a solution from the steroid composition, the bioabsorbable polymer and the solvent;

forming droplets from the solution; and

removing the solvent from the droplets to cause the droplets to form microspheres.

2. The method of claim 1, wherein the steroid composition comprises methylprednisolone acetate, triamcinolone acetonide, dexamethasone sodium phosphate, betamethasone sodium phosphate, betamethasone acetate and combinations thereof.

3. The method of claim 1, wherein the bioabsorbable polymer is fabricated from one or more of the following monomers:

lactide, glycolide, caprolactone, dioxanone, and trimethylene carbonate.

4. The method of claim 1, wherein the solvent comprises N-methylpyrrolidone, dimethylsulfoxide, formamide, dimethyl formamide or combinations thereof.

5. The method of claim 1, wherein the solvent has a high ability to dissolve the bioabsorbable polymer and the steroid composition and wherein the solvent has a low human toxicology.

6. The method of claim 1, wherein the solvent is immiscible in a first oil and miscible in a second oil and wherein forming the droplets from the solution comprises suspending the solution in the first oil to produce droplets.

7. The method of claim 6, wherein removing the solvent from the droplets to form the microspheres comprises:

adding the second oil to the first oil and the solution to form a mixture;

stirring the mixture;

removing the solvent from the droplets to form microspheres; and

collecting the microspheres on a filter.

8. The method of claim 7, and further comprising rinsing the microspheres with a second solvent.

9. The method of claim 8, wherein the second solvent is hexane.

10. The method of claim 7, wherein a ratio of the first oil to the second oil is between about 1:

3 and 1;

7.

11. The method of claim 7, wherein the second oil is rapidly added to the first oil.

12. The method of claim 7, wherein the first oil is mineral oil.

13. The method of claim 7, wherein the second oil is vegetable oil.

14. The method of claim 1, wherein the microspheres have a diameter of between about 10 micrometers and about 100 micrometers.

15. The method of claim 1, wherein the forming droplets from the solution and the removing the solvent from the droplets to cause the droplets to form microspheres spraying droplets of the solution into a first oil to produce microspheres.

16. The method of claim 15, wherein spraying the droplets is done using an aerodynamically assisted jetting device.

17. Prolonged-release injectable steroids comprising a microsphere comprising a steroid composition and a bioabsorbable polymer, wherein the steroid composition is released from the bioabsorbable polymer at a relatively constant rate that is substantially independent of a concentration of the steroid composition in the bioabsorbable polymer.

18. The prolonged-release injectable steroids of claim 17, wherein the steroid composition comprises methylprednisolone acetate, triamcinolone acetonide, dexamethasone sodium phosphate, betamethasone sodium phosphate, betamethasone acetate and combinations thereof.

19. The prolonged-release injectable steroids of claim 17, wherein the bioabsorbable polymer has a low crystallinity, low glass transition temperature, and a slow rate of bioabsorption.

20. The prolonged-release injectable steroids of claim 17, wherein the bioabsorbable polymer is fabricated from one or more of the following monomers:

lactide, glycolide, caprolactone, dioxanone, and trimethylene carbonate.

21. The prolonged-release injectable steroids of claim 17, wherein the solvent comprises N-methylpyrrolidone, dimethylsulfoxide, formamide, dimethyl formamide or combinations thereof.

22. The prolonged-release injectable steroids of claim 17, wherein the solvent has a high ability to dissolve the bioabsorbable polymer and the steroid composition and wherein the solvent has a low human toxicology.

23. The prolonged-release injectable steroids of claim 17, wherein the solvent is immiscible in a first oil and miscible in a second oil and wherein forming the droplets from the solution comprises suspending the solution in the first oil to produce droplets.

24. The prolonged-release injectable steroids of claim 17, wherein the microspheres have a diameter of between about 10 micrometers and about 100 micrometers.

25. A method of simulating drug release from a microsphere comprising:

preparing an eluant solution from 1,4-dioxane;

flowing the eluant solution past a plurality of microspheres containing a steroid composition and a bioabsorbable polymer;

eluting the drug composition from the microspheres into the eluant solution; and

collecting the eluted steroid composition.

26. The method of claim 26, wherein the steroid composition comprises methylprednisolone acetate, triamcinolone acetonide, dexamethasone sodium phosphate, betamethasone sodium phosphate, betamethasone acetate and combinations thereof.

27. The method of claim 26, wherein the bioabsorbable polymer is fabricated from one or more of the following monomers:

lactide, glycolide, caprolactone, dioxanone, and trimethylene carbonate.

28. The method of claim 26, wherein the eluant solution further comprises water and the volume ratio of 1,4-dioxane to water is between about 1:

3 to about 1;

5.

29. The method of claim 26, and further comprising maintaining the microspheres at a temperature of between about 30°

C. and about 45°

C.

30. The method of claim 26, wherein collecting the steroid composition is by flowing the eluant solution with the eluted steroid composition past a plurality of glass beads.

31. The method of claim 31, wherein the glass beads are maintained at a temperature of less than about 10°

C.