Method of spray freeze drying proteins for pharmaceutical administration

• US 6,284,282 B1
• Filed: 04/27/1999
• Issued: 09/04/2001
• Est. Priority Date: 04/29/1998
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Nguyen, Phuong-Anh, Maa, Yuh-Fun
• Primary Examiner(s): Dudash, Diana
• Assistant Examiner(s): SHARAREH, SHAHNAM J
• Application Number:
  US09/299,377
• Time in Patent Office: 861 Days
• Field of Search: 424/45, 424/489, 424/46, 424/499, 514/2, 514/12, 514/13
• US Class Current: 424/499
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• 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 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00

Abstract

The present invention relates to the spray freeze dry preparation of dry powder formulations of therapeutic proteins suitable for administration via pulmonary delivery.

Claims

1. A method of preparing a spray-freeze dried composition for pulmonary administration comprising particles of a therapeutic protein having an average physical size of 6-8 microns and an aerodynamic particle size of less than 6.8 microns, said method comprising:

(a) atomizing a liquid formulation comprising a therapeutic protein followed by freezing, wherein the freezing is accomplished by immersion into a cold fluid to prepare frozen droplets;

(b) annealing said frozen droplets;

(c) drying said droplets to form powder particles; and

(d) recovering said particles;

wherein said annealing occurs prior to said drying.

2. The method of claim 1 wherein the temperature of the cold fluid ranges from about −

200°

C. to −

80°

C.

3. The method of claim 1 wherein the temperature of the cold fluid ranges from about −

200°

C. to about −

100°

C.

4. The method of claim 3 wherein the temperature of the cold fluid is about −

200°

C.

5. The method of claim 3 wherein the temperature of the cold fluid is about −

196°

C.

6. The method of claim 5 wherein the cold fluid is liquid nitrogen.

7. The method of claim 1 wherein the drying step is done at about the same temperature as the freezing step.

8. The method of claim 1 wherein the annealing is done at a temperature from about −

10°

C. to about −

80°

C.

9. The method of claim 8 wherein the annealing is done at a temperature from about −

30°

C. to about −

60°

C.

10. The method of claim 9 wherein the annealing is done at a temperature of about −

50°

C.

11. The method of claim 10 wherein the drying is done under a vacuum and at a temperature from about −

10°

C. to about −

50°

C.

12. The method of claim 11 wherein the drying temperature is from about −

20°

C. to about −

40°

C.

13. The method of claim 12 wherein the drying temperature is at about −

25°

C.

14. The method of claim 10 wherein the drying is done to achieve a dryness of about 1-10% remaining water.

15. The method of claim 14 wherein the dryness is about 1 to about 5% remaining water.