High Pressure Compaction For Pharmaceutical Formulations

• US 20070218139A1
• Filed: 12/22/2003
• Published: 09/20/2007
• Est. Priority Date: 12/20/2002
• Status: Abandoned Application

• Current Assignee: St. James Associates LLC
• Original Assignee: St. James Associates LLC
• Inventors: Smith, Thomas, Gauzer, Gene
• Application Number:
  US10/538,991
• Publication Number:
  US 20070218139A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1688 resulting in pure drug agglomerate optionally containing up to 5% of excipient
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Abstract

Methods for producing a pharmaceutical preparation of pressure-fused particles including an active pharmaceutical ingredient are disclosed. The methods include the application of a pressure of between 0.1 GPa and 10 GPa to produce a compacted sample. The pressure-fused particles of the invention are useful for parenteral administration, and particularly sustained-release formulations, due to dissolution kinetics which are superior to conventional crystalline or amorphous packed powder preparations of active pharmaceutical ingredients. Pharmaceutical preparations including such pressure-fused microparticles are also disclosed.

Claims

1. A method for producing a pharmaceutical preparation of pressure-fused particles comprising an active pharmaceutical ingredient, the method comprising:

(a) providing a sample comprising said active pharmaceutical ingredient in crystalline or amorphous form;

(b) subjecting said sample to high pressure compaction at a pressure of between 0.1 GPa and 10 GPa to produce a compacted sample; and

(c) isolating pressure-fused particles from said compacted sample.

2. The method of claim 1, wherein said pressure is between 0.5 GPa and 7.5 GPa.

3. The method of claim 1, wherein said pressure is between 1 GPa and 5 GPa

4. The pharmaceutical preparation of claim 1, wherein said produce pressure-fused microparticles have a density of between 1 g/cm³ and 40 g/cm³.

5. The pharmaceutical preparation of claim 1, wherein said produce pressure-fused microparticles have a density of between between 2 g/cm³ and 20 g/cm³.

6. The pharmaceutical preparation of claim 1, wherein said produce pressure-fused microparticles have a density of between between 4 g/cm³ and 10 g/cm³.

7. The method of claim 1, wherein said compacted sample has a thickness of between 25 μ

m and 400 μ

m.

8. The method of claim 1, wherein said compacted sample has a thickness of between 50 μ

m and 200 μ

m;

9. The method of claim 1, wherein said compacted sample has a thickness of between 100 μ

m and 150 μ

m.

10. The method of claim 1, wherein said pressure is maintained for a period of between 30 sec. and 10 min.

11. The method of claim 1, wherein said pressure is maintained for a period of between 60 sec. and 5 min.

12. The method of claim 1, wherein said pressure is maintained for a period of between 90 sec. and 3 min.

13. The method of claim 1, wherein said pressure-fused particles have a maximum dimension between 20 μ

m and 800 μ

m.

14. The method of claim 1, wherein said pressure-fused particles have a maximum dimension between 40 μ

m and 400 μ

m.

15. The method of claim 1, wherein said pressure-fused particles have a maximum dimension between 100 μ

m and 250 μ

m.

16. The method of claim 1, wherein the step of isolating said pressure-fused particles from said compacted sample comprises sieving said compacted sample through a sieve with an exclusion limit of between 20 μ

m and 800 μ

m.

17. The method of claim 1, wherein the step of isolating said pressure-fused particles from said compacted sample comprises sieving said compacted sample through a sieve with an exclusion limit of between 40 μ

m and 400 μ

m.

18. The method of claim 1, wherein the step of isolating said pressure-fused particles from said compacted sample comprises sieving said compacted sample through a sieve with an exclusion limit of between 100 μ

m and 250 μ

m.

19. The method of claim 1, wherein said sample comprises micronized particles comprising said active pharmaceutical ingredient

20. A pharmaceutical preparation of pressure-fused particles comprising an active pharmaceutical ingredient, the pressure-fused particles comprising:

an active pharmaceutical ingredient subjected to high pressure compaction at a pressure of between 0.1 GPa and 10 GPa

21. The pharmaceutical preparation of claim 20, wherein said pressure is between 0.5 GPa and 7.5 GPa

22. The pharmaceutical preparation of claim 20, wherein said pressure is between 1 GPa and 5 GPa.

23. The pharmaceutical preparation of claim 20, wherein said produce pressure-fused microparticles have a density of between 1 g/cm³ and 40 g/cm³.

24. The pharmaceutical preparation of claim 20, wherein said produce pressure-fused microparticles have a density of between between 2 g/cm³ and 20 g/cm³.

25. The pharmaceutical preparation of claim 20, wherein said produce pressure-fused microparticles have a density of between between 4 g/cm³ and 10 g/cm³.

26. The pharmaceutical preparation of claim 20, wherein said pressure-fused particles have a maximum dimension between 20 μ

m and 800 μ

m.

27. The pharmaceutical preparation of claim 20, wherein said pressure-fused particles have a maximum dimension between 40 μ

m and 400 μ

m.

28. The pharmaceutical preparation of claim 20, wherein said pressure-fused particles have a maximum dimension between 100 μ

m and 250 μ

m.