Process for making micro-sized protein particles

1. A process of making micro-sized protein particles comprising the steps of:

precipitating nano-sized protein particles from a precipitant solution under conditions to form a suspension of nano-sized protein particles in a liquid medium, said nano-sized protein particles having a narrow particle size distribution with a span value of less than 3; and

spray-drying the nano-sized protein particles suspension under conditions to agglomerate the nano-sized protein particles and thereby form micro-sized protein particles having a porous structure, wherein the micro-sized protein particles are suitable for use as a formulation for pulmonary delivery.

2. The process of making micro-sized protein particles as claimed in claim 1 , wherein said precipitating step comprises the step of micro-mixing a precipitant solution and an anti-solvent.

3. The process of making micro-sized protein particles as claimed in claim 1 , wherein said protein is selected from the group consisting of insulin, albumin, parathyroid hormone, gonadotropin-releasing hormone, DNAse, cyclosporin, immunoglobulin, erythropoietin, interferon, colony stimulating factor, growth hormone, luteinising-hormone releasing hormone (LHRH) analog, LHRH antagonist, tissue plasminogen activator, somatostatin analog, r Factor VIII, r Factor IX, calcitonin, abciximab, dornase alfa, bone inducing protein, bone morphogenic protein, brain derived growth factor, gastrin 17 immunogen, interleukins, polymerase enhancing factor superoxide, chimeric monoclonal antibody, permeability increasing protein-21, platelet derived growth factor, stem cell factor, recombinant human thyrotropin alfa, somatomedin C and mixtures thereof.

4. The process of making micro-sized protein particles as claimed in claim 1 , wherein said suspended nano-sized protein particles in said liquid medium is atomized to form droplets during said spray-drying step.

5. The process of making micro-sized protein particles as claimed in claim 4 , wherein the time taken to dry said droplet is less than 10 seconds.

6. The process of making micro-sized protein particles as claimed in claim 1 , wherein said suspended nano-sized protein particles have a % solids concentration in the range of 0.1% to 10% in said liquid medium.

7. The process of making micro-sized protein particles as claimed in claim 1 , wherein the temperature of said suspended nano-sized protein particles is in the range of 4° C. to 40° C.

8. The process of making micro-sized protein particles as claimed in claim 1 , wherein said nano-sized protein particles have a particle size in the range of 50 nm to 500 nm.

9. The process of making micro-sized protein particles as claimed in claim 2 , wherein said micro-mixing is undertaken under high shear conditions.

10. The process of making micro-sized protein particles as claimed in claim 9 , wherein said high shear condition is characterized by a Reynold's number in the range of 2000 to 200,000.

11. The process of making micro-sized protein particles as claimed in claim 1 , wherein said spray-drying step is undertaken without the use of a binder to agglomerate said nano-sized protein particles.

12. The process of making micro-sized protein particles as claimed in claim 1 , wherein said protein is biologically active to a target.

13. The process of making micro-sized protein particles as claimed in claim 12 , wherein said spray-drying does not substantially degrade the biologically activity of said protein.

14. The process of making micro-sized protein particles as claimed in claim 12 , further comprising a protein that is not biologically active to a target.

15. A micro-sized protein particle having a porous structure and comprised of a plurality of agglomerated nano-sized protein particles, said nano-sized protein particles having a narrow particle size distribution with a span value of less than 3, wherein the micro-sized protein particle is suitable for use as a formulation for pulmonary delivery.

16. The micro-sized protein particle as claimed in claim 15 , wherein said micro-sized protein particle has a particle size in the range from 1 μm to 10 μm.

17. The micro-sized protein particle as claimed in claim 15 , wherein said micro-sized protein particle has a substantially spherical shape.

18. The micro-sized protein particle as claimed in claim 15 , wherein the porosity of said micro-sized protein particle is in the range of 10% to 80%.

19. The micro-sized protein particle as claimed in claim 15 , wherein said micro-sized protein particle has a porous inner core.

20. The micro-sized protein particle as claimed in claim 15 , wherein said micro-sized protein particle has a void in the inner core.