Apparatus and process to produce particles having a narrow size distribution and particles made thereby

• US 20020071871A1
• Filed: 07/31/2001
• Published: 06/13/2002
• Est. Priority Date: 08/01/2000
• Status: Abandoned Application

• Current Assignee: Novartis Pharma AG (Novartis Ag)
• Original Assignee: Novartis Pharma AG (Novartis Ag)
• Inventors: Snyder, Herm, Nasiatka, Jim, Smith, Adrian E.
• Application Number:
  US09/919,278
• Publication Number:
  US 20020071871A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Abstract

The present invention is directed to particles, including liquid droplets and dry particulates, having a narrow particle size distribution made from a liquid feed stock. In particular, the invention is directed to producing particles of a desired median diameter and narrow particle size distribution without the need for additional separation processing. The process of the present invention can be tailored to produce substantially monodisperse particles or multimodal particles having well defined and controllable particle size distributions. The present invention is particularly well suited for producing particles for pulmonary administration.

Claims

1. A method for making particles from a liquid feed stock containing a pharmaceutical agent to produce particles suitable for pulmonary administration having a narrow particle size distribution comprising:

providing a feed stock comprising a pharmaceutically active agent and a solvent;

forcing said feed stock into a manifold defined between a vibratable element and a plate and forcing the feed stock through the plate, said plate comprising holes of at least one predetermined diameter, in order to produce droplets comprising a droplet size distribution wherein at least 80% of the droplets have a diameter within ±

25% of the median droplet diameter;

removing solvent from said droplets to produce particles suitable for pulmonary administration.

2. A method according to claim 1 further comprising vibrating said vibratable element in order to force said feed stock through the plate and produce droplets.

3. A method according to claim 2 wherein a piezoelectric element is coupled to said vibratable element.

4. A method according to claim 1 wherein said holes comprise a predetermined diameter of less than 30 microns.

5. A method according to claim 4 wherein said holes comprise a predetermined diameter of less than 10 microns.

6. A method according to claim 1 wherein said plate comprises holes having a first diameter of less than 30 microns and a second series of holes having a second diameter of ±

50% of said first diameter.

7. A method according to claim 6 wherein said second diameter is within ±

20% of said first diameter.

8. A method according to claim 7 wherein said first diameter is less than 10 microns.

9. A method according to claim 1 wherein said atomizer is provided with said feed stock at a feed rate of 5 ml/mn−

3500 ml/mn.

10. A method according to claim 1 wherein said particles are porous.

11. A method according to claim 1 wherein said particles comprise a MMD of less than 10 microns and a MMAD of 1-5 microns.

12. A method according to claim 1 wherein said particles comprise a particle size distribution wherein at least 90% of the particles have a diameter within a range of less than 4 microns.

13. A method according to claim 1 wherein at least 90% of the droplets have a diameter within ±

25% of the median droplet diameter.

14. A method according to claim 1 wherein at least 95% of the mass of the droplets have a diameter within ±

25% of the median droplet diameter.

15. A method according to any one of claims 1, 13, or 14 wherein the droplets have a diameter is within ±

15% of the median droplet diameter.

16. A method according to claim 15 wherein the droplets have a diameter within ±

8% of the median droplet diameter.

17. A method according to claim 1 wherein said solvent is removed by heating said droplets in a gas stream to produce dried particles.

18. A method according to claim 17 wherein said dried particles are collected.

20. A method according to claim 19 wherein the dried particles comprise a particle size distribution wherein at least 80% of the mass of the particles have a diameter within a 4 micron range.

21. A method according to claim 19 wherein the dried particles comprise a particle size distribution wherein at least 90% of the mass of the particles have a diameter within a 4 micron range.

24. A method according to claim 19 further comprising vibrating said vibratable element in order to force said feed stock through the plate and produce droplets.

26. A method according to claim 19 wherein said holes comprise a predetermined diameter of less than 30 microns.

27. A method according to claim 19 wherein said plate comprises holes having a first diameter of less than 30 microns and a second series of holes having a second diameter of ±

50% of said first diameter.

30. A method according to claim 19 wherein said particles are porous.

31. A method according to claim 19 wherein said particles comprise a MMD less than 10 microns and a MMAD 1-5 microns.

19. A method for spray drying a feed stock containing a pharmaceutical agent to produce particles suitable for pulmonary administration having a narrow particle size distribution comprising:

providing a feed stock comprising a pharmaceutically active agent at a flow rate of at least 5 ml/min;

forcing said feed stock into a manifold defined between a vibratable element and a plate and forcing the feed stock through the plate, said plate comprising holes of at least one predetermined diameter, in order to produce droplets;

drying said droplets in a gas stream to produce dried particles comprising a particle size distribution wherein at least 70% of the mass of the particles have a diameter within a 4 micron range; and

collecting said dried particles.

22. A method according to any one of claims 19-21 wherein the dried particles have a diameter within a 3 micron range.

23. A method according to any one of claims 19-21 wherein the dried particles have a diameter within a 1.5 micron range.

25. A method according to claim 24 wherein said plate is vibrated by coupling a piezoelectric element to said plate.

28. A method according to claim 27 wherein said second diameter is within ±

20% of said first diameter.

29. A method according to claim 28 wherein said first diameter is less than 10 microns.