Claims
- 1. A process for preparing solid particles of a pharmaceutical agent, comprising the steps of:
(a) forming first particles of a first size, said first particles comprising
an admixture of a pharmaceutical agent and a macromolecular carrier, said carrier capable of existing as a solid and said admixture having a first glass transition temperature, and admixed plasticizer, said plasticizer lowering the first glass transition temperature of the admixture to a second glass transition temperature which is below the first glass transition temperature; (b) maintaining said first particles at a temperature above the second glass transition temperature for a time period adequate to cause the first particles to shrink and/or collapse to second particles of a second size, which second size is smaller than the first size; (c) removing plasticizer from the second particles to yield modified second particles thereby raising the glass transition temperature from said second glass transition temperature to a third glass transition temperature which is higher than second glass transition temperature; (d) recovering the modified second particles; and (e) storing said modified second particles at a temperature below the third glass transition temperature as the desired solid particles of the pharmaceutical agent.
- 2. The process of claim 1, wherein said macromolecular carrier comprises a naturally-occurring macromolecular material.
- 3. The process of claim 1, wherein said macromolecular carrier comprises a polysaccharide.
- 4. The process of claim 1, wherein said macromolecular carrier comprises a polypeptide.
- 5. The process of claim 1, wherein said macromolecular carrier comprises a synthetic polymer.
- 6. The process of claim 1, wherein said pharmaceutical agent is a pharmaceutically active protein.
- 7. The process of claim 1, wherein said pharmaceutical agent is a small molecule drug.
- 8. The process of claim 1, wherein said pharmaceutical agent is a polynucleotide.
- 9. The process of claim 1, wherein the particles are formed in step (a) by spray-drying.
- 10. The process of claim 1, wherein the particles are formed in step (a) by spray freeze-drying.
- 11. The process of claim 1, wherein the particles are formed in step (a) by grinding or milling.
- 12. The process of claim 1, wherein the plasticizer is removed in step (c) by evaporation and/or washing.
- 13. The process of claim 1, wherein the modified second particles are stored in step (e) at ambient temperature.
- 14. A process for preparing solid particles of a pharmaceutical agent, comprising the steps of:
(a) forming an admixture comprising a pharmaceutical agent and macromolecular carrier, said admixture having a first glass transition temperature; (b) forming particles of a first size of said admixture; (c) adding plasticizer to said particles of a first size to yield plasticized particles, said plasticizer lowering the glass transition temperature of the admixture to a second glass transition temperature below said first glass transition temperature; (d) maintaining said plasticized particles at a temperature above said second glass transition temperature for a time period adequate to cause said plasticized particles to shrink and/or collapse to particles of a second size which second size is smaller than the first size; (e) removing plasticizer from the particles of a second size to yield modified particles of a second size thereby raising the glass transition temperature from said second glass transition temperature to a third glass transition temperature which is higher than second glass transition temperature; (f) recovering the modified particles of a second size; and (g) storing said modified particles of the second size at a temperature below the third glass transition temperature as the desired solid particles of the pharmaceutical agent.
- 15. The process of claim 14, wherein said macromolecular carrier comprises a naturally-occurring macromolecular material.
- 16. The process of claim 14, wherein said macromolecular carrier comprises a polysaccharide.
- 17. The process of claim 14, wherein said macromolecular carrier comprises a polypeptide.
- 18. The process of claim 14, wherein said macromolecular carrier comprises a synthetic polymer.
- 19. The process of claim 14, wherein said pharmaceutical agent is a pharmaceutically active protein.
- 20. The process of claim 14, wherein said pharmaceutical agent is a small molecule drug.
- 21. The process of claim 14, wherein said pharmaceutical agent is a polynucleotide.
- 22. The process of claim 14, wherein the particles are formed in step (b) by spray drying.
- 23. The process of claim 14, wherein said particles are formed in step (b) by spray freeze-drying.
- 24. The process of claim 14, wherein the particles are formed in step (b) by grinding or milling.
- 25. The process of claim 14, wherein the plasticizer is removed in step (e) by evaporation and/or washing.
- 26. The process of claim 14, wherein the modified particles of the second size are stored in step (g) at ambient temperature.
- 27. A process for preparing solid particles of a pharmaceutical agent, comprising the steps of:
(a) forming an admixture comprising a pharmaceutical agent, a macromolecular carrier and plasticizer;
said pharmaceutical agent and said macromolecular carrier having a first glass transition temperature when separately admixed; and said pharmaceutical agent, said macromolecular carrier and said plasticizer having a second glass transition temperature when together admixed, said second glass transition temperature being below said first glass transition temperature; (b) forming first particles of a first size of said admixture; (c) maintaining said first particles of a first size at a temperature above said second glass transition temperature for a time period adequate to cause said first particles to shrink and/or collapse to particles of a second size which second size is smaller than the first size; (d) removing plasticizer from the particles of a second size to yield modified particles of a second size thereby raising the glass transition temperature from said second glass transition temperature to a third glass transition temperature which is higher than second glass transition temperature; (e) recovering the modified particles of a second size; and (f) storing said modified particles of the second size at a temperature below the third glass transition temperature as the desired solid particles of the pharmaceutical agent.
- 28. The process of claim 27, wherein said macromolecular carrier comprises a naturally-occurring macromolecular material.
- 29. The process of claim 27, wherein said macromolecular carrier comprises a polysaccharide.
- 30. The process of claim 27, wherein said macromolecular carrier comprises a polypeptide.
- 31. The process of claim 27, wherein said macromolecular carrier comprises a synthetic polymer.
- 32. The process of claim 27, wherein said pharmaceutical agent is a pharmaceutically active protein.
- 33. The process of claim 27, wherein said pharmaceutical agent is a small molecule drug.
- 34. The process of claim 27, wherein said pharmaceutical agent is a polynucleotide.
- 35. The process of claim 27, wherein the particles are formed in step (b) by spray drying.
- 36. The process of claim 27, wherein the particles are formed in step (b) by spray freeze-drying.
- 37. The process of claim 27, wherein the particles are formed in step (b) by grinding or milling.
- 38. The process of claim 27, wherein the plasticizer is removed in step (d) by evaporation and/or washing.
- 39. The process of claim 27, wherein the modified particles of the second size are stored in step (f) at ambient temperature.
- 40. Solid particles of a pharmaceutical agent prepared by a process comprising the steps of:
(a) forming first particles of a first size, said first particles comprising
an admixture of a pharmaceutical agent and a macromolecular carrier, said carrier capable of existing as a solid and said admixture having a first glass transition temperature, and admixed plasticizer, said plasticizer lowering the first glass transition temperature of the admixture to a second glass transition temperature which is below the first glass transition temperature; (b) maintaining said first particles at a temperature above the second glass transition temperature for a time period adequate to cause the first particles to shrink and/or collapse to second particles of a second size, which second size is smaller than the first size; (c) removing plasticizer from the second particles to yield modified second particles thereby raising the glass transition temperature from said second glass transition temperature to a third glass transition temperature which is higher than second glass transition temperature; (d) recovering the modified second particles; and (e) storing said modified second particles at a temperature below the third glass transition temperature as the desired solid particles of the pharmaceutical agent.
- 41. Solid particles according to claim 40 prepared by a process comprising the steps of:
(a) forming an admixture comprising a pharmaceutical agent and macromolecular carrier, said admixture having a first glass transition temperature; (b) forming particles of a first size of said admixture; (c) adding plasticizer to said particles of a first size to yield plasticized particles, said plasticizer lowering the glass transition temperature of the admixture to a second glass transition temperature below said first glass transition temperature; (d) maintaining said plasticized particles at a temperature above said second glass transition temperature for a time period adequate to cause said plasticized particles to shrink and/or collapse to particles of a second size which second size is smaller than the first size; (e) removing plasticizer from the particles of a second size to yield modified particles of a second size thereby raising the glass transition temperature from said second glass transition temperature to a third glass transition temperature which is higher than second glass transition temperature; (f) recovering the modified particles of a second size; and (g) storing said modified particles of the second size at a temperature below the third glass transition temperature as the desired solid particles of the pharmaceutical agent.
- 42. Solid particles according to claim 40 prepared by a process comprising the steps of:
(a) forming an admixture comprising a pharmaceutical agent, a macromolecular carrier and plasticizer; said pharmaceutical agent and said macromolecular carrier having a first glass transition temperature when separately admixed; and said pharmaceutical agent, said macromolecular carrier and said plasticizer having a second glass transition temperature when together admixed, said second glass transition temperature being below said first glass transition temperature; (b) forming first particles of a first size of said admixture; (c) maintaining said first particles of a first size at a temperature above said second glass transition temperature for a time period adequate to cause said first particles to shrink and/or collapse to particles of a second size which second size is smaller than the first size; (d) removing plasticizer from the particles of a second size to yield modified particles of a second size thereby raising the glass transition temperature from said second glass transition temperature to a third glass transition temperature which is higher than second glass transition temperature; (e) recovering the modified particles of a second size; and (f) storing said modified particles of the second size at a temperature below the third glass transition temperature as the desired solid particles of the pharmaceutical agent.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is related to U.S. provisional patent application serial No. 60/296,987, filed Jun. 8, 2001, from which application priority is claimed pursuant to 35 U.S.C. §119(e)(1) and which application is incorporated herein by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60296987 |
Jun 2001 |
US |